Fall In Glomerular Filtration Rate Research Articles

Chronic Kidney Disease: Decreasing Serum Klotho Levels Predict Adverse Renal and Vascular Outcomes.

Background and Objectives: Soluble alpha Klotho (s.Klotho) is an emerging marker for chronic kidney disease (CKD) prognosis. The objective was to study the association between s.Klotho and CKD-related decrease in glomerular filtration rate (GFR), bone and vascular damage. Method: A total of 118 patients with CKD stage 2-4 were enrolled and 107 patients continued in the study. Clinical and laboratory parameters were recorded at time of enrollment and 12 months. A double sandwich ELISA for s.Klotho was recorded in controls (n = 25) and patients' serum samples at 6 months (n = 107) and 12 months (n = 102). Primary endpoints like 40% or more fall in GFR, a requirement for renal replacement therapy (RRT), and death with different grades of s.Klotho deficiency were studied. Results: Of the 107 patients (80 male and 27 female), mean s.Klotho was 3.46 ng/mL (02.3-04.2). The GFR fall was significantly different (p value < 0.0001) in the different grades of s.Klotho deficiency with Grade 4 s.Klotho deficiency (0.1-2.99 ng/mL) having the maximum fall of GFR at 9.2 mL/min/1.73 m2 (04.8-12.0) and minimum in Grade 2 (3-5.99 ng/mL) at 1.35 mL/min/1.73 m2 (03.0-02.75). The Ankle Brachial Pressure Index positively correlated with s.Klotho and the correlation coefficient was 0.536 (0.382-0.662) (p < 0.001). The carotid intimal medial thickness negatively correlated with s.Klotho and the correlation coefficient was -0.712 (95% CI: -0.797--0.601, p < 0.001). All five deaths had s.Klotho Grade 4 (severe) deficiency. The event-free survival rate was maximum (100%) in Grade 2 Klotho deficiency and lowest (55%) in Grade 4 s.Klotho deficiency. Conclusions: s.Klotho levels decreased significantly in patients with progressive kidney failure. s.Klotho levels significantly correlated with the presence of vascular disease. Death and need for RRT were significantly more in patients with severe s.Klotho deficiency.

#4511 TOLVAPTAN DOSE ADJUSTMENT IN ADPKD BASED ON URINARY OSMOLALITY: SIMILAR EFFICACY AND LOW DROPOUT RATE

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease. Tolvaptan is the only treatment that has been shown to slow disease progression. The current recommendation is to reach the maximum tolerated dose while controlling side effects such as hepatotoxicity. There are data suggesting a marked decrease in tolerability at high doses of the drug. We explored the possibility of an individualized tolvaptan dose adjustment, based on urinary osmolality (Uosm), as an indirect indicator of treatment efficacy. Method Single-center prospective cohort study of tolvaptan in patients with ADPKD and rapid progression, with dose adjustment according to Uosm, with dose increase if Uosm &amp;gt; 200 mOsm/kg. Glomerular filtration rate (GFR) estimated by CKD-EPI, Uosm, adverse effects and dropouts were analyzed. Results 40 patients: 35 patients with more than 2 years treatment, mean follow-up 30± 6 months. Mean age 45± 7 years, 82% hypertensive and 47% male. Evolution: mean annual fall in GFR during the previous 3 years without treatment -7.24 ± 1.5 ml/min/year. Baseline GFR 51.05±12.5 mL/min and baseline Uosm 391±87 mOsm/kg. Average annual drop in GFR over 3 years with treatment -3.18±1.3 mL/min/year. Average Uosm achieved during treatment 171 ± 47 mOsm/kg. Maximum tolvaptan dose reached 60 mg (90%) and 90 mg (10%). The adverse events recorded highlight that there were no cases of hepatotoxicity (0%). The most frequent alterations were hyperuricemia (18%) and hypernatremia (11%), but in all cases asymptomatic. Polyuria was recorded in all our patients (100%), with a median diuresis 6000 ml/day (7000-5500), but the dropout rate due to aquaretic effects was minimal, only 2 patients (5%). Conclusion In our series of patients, treatment with tolvaptan at a dose adjusted to Uosm, seems to show similar efficacy to the reference studies in the annual fall of GFR, with a low rate of adverse events and very low dropout rate.

Serum level of hepcidin in chronic kidney disease - A hospital-based study from South India

Background: The term “chronic kidney disease (CKD)” refers to a variety of pathophysiologic conditions characterized by impaired kidney function and a steady fall in glomerular filtration rate. CKD is a slowly progressive silent epidemic that affects approximately 12% of the world population. Aims and Objectives: The aim of the study was to estimate the level of serum Hepcidin in patients with CKD compared to healthy controls. Materials and Methods: Hundred subjects both male and female over the age of 18 were included in the study and informed consent was obtained from each of them. The study population was divided equally into two groups. Blood serum was collected to estimate level of hepcidin, urea, creatinine, ferritin, iron, total iron binding capacity, hs C-reactive protein (CRP), and total proteins. Urine was collected in a sterile container for urine protein creatinine ratio. Results: Hepcidin could be a prognostic marker in the clinical outcome of CKD especially in the progression of CKD. There was a highly significant positive correlation of serum Hepcidin with hsCRP, ferritin, creatinine, urea, urine protein creatinine ratio, and erythrocyte sedimentation rate. Significant negative correlation of serum Hepcidin with Creatinine Clearance, Iron, TIBC, Transferrin saturation, Hemoglobin, and Total Proteins had been observed. Conclusion: The current study showed that patients with CKD and anemia have considerably higher serum hepcidin concentrations. The level of hepcidin increases as disease progresses in CKD patients. Hepcidin, mediator of anemia in CKD is the potential target to treat anemia in them to prevent death due to cardiovascular complications and improve their quality of life.

End-proximal tubule phosphate concentration increases as GFR falls in humans: measurement by means of a lithium clearance-based methodology.

Microscopic nephrocalcinosis secondary to intratubular calcium phosphate (CaP) precipitation is thought to accelerate progression to end-stage renal failure in chronic kidney diseases. In phosphorus (P)-loaded uninephrectomized rats, intratubular CaP crystal formation and progressive tubular damage occurred when end-proximal tubule P concentration (ePTpc) increased above a threshold level. We have calculated ePTpc in humans by urine P and creatinine concentration, with the end-proximal tubule fluid volume calculated either as lithium (Li) clearance (ePTpc-Li) or as a fixed 0.7 fraction of glomerular filtration rate (GFR), as published (ePTpc-70). Healthy people undergoing living transplant kidney donation before (DON-pre, n=70) and after (DON-post, n=64) nephrectomy and 25 patients with stage 2-5 CKD were investigated while on regular free diet. ePTpc showed a stepwise increase with decreasing functional renal mass (DON-pre 2.51±0.99 and 1.56± 0.47 mg/dL for ePTpc-Li and -70 calculation, respectively; DON-post 3.43±1.14and 2.18±0.44; CKD 5.68±3.30and 3.00±1.30, P<.001 for all); ePTpc was inversely correlated with Ccr and directly with PTH, fractional P excretion and excretion (UpV) corrected for GFR (P<.001 for all), but not with Pp. ePTpc-Li and ePTpc-70 were significantly correlated (r=0.62, P<.001), but ePTpc-70 was lower than the corresponding ePTpc-Li. Levels of ePTpc increased above a suggested dangerous threshold when daily UpV/GFR was higher than about 10mg/mLCcr. ePTpc progressively increases in humans as functional renal mass falls independently from plasma P levels. Main determinants of ePTpc rise are GFR fall, degree of phosphaturia per unit GFR and P intake corrected for GFR. It may become a novel, potentially useful, indicator to guide management of CKD patients.

Preserved renal function during long-term follow-up in children with chronic liver disease.

AimWe have previously found well‐maintained renal function in children with new‐onset chronic liver disease. In this study, we investigated their renal function during long‐term follow‐up of the disease.MethodsIn a study of 289 children with chronic liver disease, renal function was investigated as glomerular filtration rate (GFR) measured as clearance of inulin or iohexol. Yearly change in GFR was calculated based on a linear mixed model. The data were analysed with regard to different subgroups of liver disease and with regard to the outcome.ResultsThe initially well‐preserved renal function remained so in most patients during the observation period, even in children with progressive liver disease leading to decompensation. The greatest fall in GFR occurred in patients with initial hyperfiltration. Cholestasis seemed to have a nephroprotective effect.ConclusionChronic liver disease in childhood seems to have less impact on renal function than believed earlier, at least as long as the liver function remains compensated. Regular renal check‐ups remain an essential tool for optimal patient care. Hyperfiltration seems to predict decline in renal function. Otherwise no further reliable prognostic markers were found in patients whose liver disease was not decompensated.

Hyperchloremia on Admission to Pediatric Intensive Care in Mechanically Ventilated Children is Associated with Impaired Renal Function.

Objective There is recent interest in the association between hyperchloremic metabolic acidosis and adverse outcomes. In vitro, hyperchloremia causes renal vasoconstriction and fall in glomerular filtration rate (GFR). The objective of this retrospective, observational study is to examine associations between chloride level at admission to pediatric intensive care (PICU) and worst GFR and requirement for renal replacement therapy. Materials and Methods All admissions to PICU between 2009 and 2019 who received invasive mechanical ventilation and had blood gas analysis performed were included. Data analyzed included patient characteristics (age, gender, diagnosis, pediatric index of mortality [PIM]-2 score); results of initial blood gas; and maximum serum creatinine (then used to calculate minimum GFR). Primary outcome measure was worst GFR during PICU stay. Secondary outcome measures were requirement for renal replacement therapy and PICU mortality. Multivariable regression analysis was used to assess if admission chloride level was independently predictive of minimum GFR during PICU stay and to examine associations between hyperchloremia (>110 mEq/L) at admission and requirement for renal replacement therapy after adjustment for confounders. Results Data were available for 2,217 patients. Median age was 16.4 months and 39% of patients were hyperchloremic at admission to PICU. Admission chloride level was independently predictive of worst GFR during PICU stay after adjustment for known confounders. Patients with hyperchloremia were not more likely to require renal replacement therapy or die than patients with normochloremia. Conclusion Prospective studies are necessary to determine if high chloride, specifically chloride containing resuscitation fluids, have a causal relationship with poor outcomes.

Renovascular hypertension in pediatric patients: update on diagnosis and management

Renovascular hypertension (RVH) is defined as an elevated blood pressure caused by kidney hypoperfusion, generally as a result of anatomic stenosis of the renal artery with consequent activation of the Renin Angiotensin-Aldosterone System. The main causes include genetic and inflammatory disorders, extrinsic compression, and idiopathic alterations. RVH is often asymptomatic and should be suspected in any child with refractory hypertension, especially if other suggestive findings are present, including those with severe hypertension, abdominal bruit, and abrupt fall of glomerular filtration rate after administration of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. There is a consensus that digital subtraction angiography is the gold standard method for the diagnosis of RVH. Nevertheless, the role of non-invasive imaging studies such as Doppler ultrasound, magnetic resonance angiography, or computed tomographic angiography remains controversial, especially due to limited pediatric evidence. The therapeutic approach should be individualized, and management options include non-surgical pharmacological therapy and revascularization with percutaneous transluminal renal angioplasty (PTRA) or surgery. The prognosis is related to the procedure performed, and PTRA has a higher restenosis rate compared to surgery, although a decreased risk of complications. This review summarizes the causes, physiopathology, diagnosis, treatment, and prognosis of RVH in pediatric patients. Further studies are required to define the best approach for RVH in children.

Increase in Bioavailability of Nitric Oxide After Renal Denervation Improves Kidney Function in Sheep With Hypertensive Kidney Disease

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P0908FGF-23, MBD AND INFLAMMATION IN CKD

Abstract Background and Aims Systemic inflammation, as well as Mineral and Bone Disease, are seen to be inherent complications of CKD, tightly related to cardio-vascular disease, protein-energy wasting and general mortality. It remains an actual problem to study relation between systemic inflammation and CKD-MBD. The aim of the study was to evaluate serum concentrations of c-terminal FGF-23 as an early marker of CKD MBD, Il-1 β, Il-6, Il-8 as inflammatory markers, and to establish relationships between FGF-23 and IL-1 β, Il-6, Il-8. Method The study involved 106 patients with CKD stages from 1 to 4, 47 women (44%) and 59 men (56%) aged from 35 to 72, mean (49.6± 13.9) years. The C-terminal FGF-23 fragment was determined using a set of reagents for the enzyme immunoassay «Biomedica». Concentration of IL-1β, IL-6 and IL-8 was determined using an assay «Vector BEST». The glomerular filtration rate (GFR) was calculated using the CKD EPI formula (KDIGO 2012). Results A progressive growth in FGF-23 levels was observed simultaneously with GFR decrease in patients with CKD. IL-1 concentration increased from CKD stage 1 ((12.64±4.30) pg/ml) to 4 ((32.06±7.86) pg/ml) (p &amp;lt;0.05) accordingly GFR fall, as well as the level of IL-6 ((7.25±2.14) pg/ml to (46.27±10,06)pg/ml) and Il-8 ((9.39±1.62) pg/ml to (33.00±9.17)pg/ml). The existence of a strong direct association (r = 0.84, p &amp;lt;0.05) between the level of Il-6 and FGF-23 in CKD stages 1-4 was established. IL-1 and Il-8 were found to have a medium strength assotiation (r=0.45, p &amp;lt;0.05 and r=0.57, p &amp;lt;0.05, accordingly) with FGF-23 concentration in patients with CKD stages 2-4. Conclusion The increase in the concentration of inflammatory factors along with progression of chronic renal failure was revealed. The existence of a strong link between the level of IL-6 and the C-terminal fragment of FGF-23 in CKD was established. Finding out the issue of the primary stimulation factor of FGF-23 production in CKD requires further research.

SUN-292 Life-Threatening Hypernatremia in Partial Diabetes Insipidus with Adipsia Due to Cranial Radiation: Diagnostic and Therapeutic Challenges

Background: Anterior pituitary dysfunction is a known, time and dose dependent effect of cranial radiotherapy but central diabetes insipidus (CDI) has been rarely reported. We present a patient with partial CDI (PCDI) and adipsia, months after subtotal resection and radiation therapy for a large anterior cranial fossa meningioma. Clinical Case: A 53-year-old woman with history of subtotal resection of a 7 cm meningioma ~2 years ago and radiation therapy (54 Gy, completed 15 months ago), was admitted to the ICU with obtundation, tachycardia (120/min), hypotension (87/52 mmHg, on vasopressors in the first 24 hours), severe hypernatremia (serum Na 170 mmol/L), and acute kidney injury (creatinine 2.11 mg/dL; baseline 1.0 mg/dL). Plasma osmolality (pOSM) was 385 mOsm/kg and urine osmolality (uOSM) was 982 mOsm/kg. MRI brain 3 months ago showed frontal lobe encephalomalacia, residual meningioma at the planum sphenoidale (1.8x3.5x2.8 cm) with cavitary lesion compatible with post-radiation necrosis. After receiving 4 litres (L) isotonic fluids and 5 L hypotonic fluids in the first 38 hours, serum Na was 168 mmol/L, creatinine 1.35 mg/dl and uOSM 386 mOsm/kg. Urine output was 2.6 L on day-1 and 1.9 L during first 7 hours on day-2. After an IV dose of 2 mcg DDAVP, uOSM increased to 784 mOsm/kg, and Na decreased to 164 mmol/L, supporting CDI diagnosis. ACTH stimulation test was normal. Levothyroxine 50 mcg daily was started for central hypothyroidism. By day-6, her mental status returned to baseline (alert only to person). DDAVP dose adjustment was challenging due to frequent fluctuation in her serum Na (130s to 150s), adipsia and urinary incontinence. On day-44, she was discharged on subcutaneous (subQ) DDAVP 0.25 mcg every 36 hours, with a serum Na of 145 mmol/L. She was readmitted 3 days later with serum Na of 164 mmol/L, followed by another prolonged hospitalization complicated by acute kidney injury and popliteal DVT. On day-64, she was discharged to a nursing facility on DDAVP 0.25 mcg subQ twice daily. Clinical Lesson: Delayed PCDI with adipsia is an exceedingly rare but challenging complication of cranial radiation therapy. The initial uOSM (twice as high as pOSM) in our case caused a delay in diagnosis. This could reflect enhanced antidiuretic response to low circulating ADH levels, possibly due to lower rate of solute extraction in dehydration, upregulation of ADH receptors due to chronic hormone deficiency, and to a fall in glomerular filtration rate. Decrease in uOSM after hydration could be due to ADH exhaustion.

Pathophysiology of Contrast-Induced Acute Kidney Injury (CIAKI).

Contrast-induced acute kidney injury (CIAKI) is a severe complication associated with the use of iodinated contrast media (CM); a sudden but potentially reversible fall in glomerular filtration rate (GFR) typically occurring 48-72 hours after CM administration. Principal risk factors related with the presentation of CIAKI are preexisting chronic kidney disease and diabetes mellitus. Studies on CIAKI present considerable complexity because of differences in CM type and dose, controversies in definition and baseline comorbidities. Despite that, it should be noted that CIAKI poses a serious health problem because it is a very common cause of hospitalacquired AKI, linked to increased morbidity and mortality and utilizing growing healthcare resources. The pathogenesis of CIAKI is heterogeneous and, thus, is incompletely understood. Three basic mechanisms appear to simultaneously occur for CIAKI development: Renal vasoconstriction and medullary hypoxia, tubular cell toxicity and reactive oxygen species formation. The relative contribution of each one of these mechanisms is unknown but they ultimately lead to epithelial and endothelial cell apoptosis and GFR reduction. Further research is needed in order to better clarify CIAKI pathophysiology and accordingly introduce effective preventive and therapeutic strategies.

Renal Nerve Deafferentation Attenuates the Fall in GFR during Intravenous Infusion of Furosemide in Anesthetized Rats

Introduction: Furosemide reduces the glomerular filtration rate (GFR) and increases the renal vascular resistance (RVR) despite inhibiting tubuloglomerular feedback but increases proximal tubule pressure, renin release, and renal nerve activity. Objective: This study tested the hypothesis that the fall in GFR with furosemide is due to volume depletion or activation of angiotensin type 1 (AT1) receptors or renal nerves. Methods: Furosemide was infused for 60 min at 1.0 mg·kg⁻¹·h⁻¹ in groups of 5–8 anesthetized rats. Additional groups received intravenous volume replacement to prevent fluid and Na⁺ losses or volume replacement plus losartan or plus sham denervation or plus renal denervation or renal nerve deafferentation. Results: At 60 min of infusion, furosemide alone reduced the GFR (–37 ± 4%; p < 0.01). This fall was not prevented by volume replacement or pretreatment with losartan, although losartan moderated the increase in RVR with furosemide (+44 ± 3 vs. +82 ± 7%; p < 0.01). Whereas the GFR fell after furosemide in rats after sham procedure (–31 ± 2%), it was not changed significantly after prior renal deafferentation. Proximal tubule pressure increased significantly but returned towards baseline over 60 min of furosemide, while urine output remained elevated, and GFR and renal blood flow depressed. Conclusions: The fall in GFR over 60 min of furosemide infusion is independent of volume depletion or activation of AT1 receptors but is largely dependent on renal afferent nerves.

Punctures versus shocks: a comparison of renal functional and structural changes after percutaneous nephrolithotomy and shockwave lithotripsy for solitary renal stone

Objective: To evaluate renal functional and structural changes following percutaneous nephrolithotomy and shockwave lithotripsy for solitary non-obstructing non-staghorn renal stone. Materials and methods: Patients with solitary unilateral non-staghorn renal stones who were planned for percutaneous nephrolithotomy (20 patients) and shockwave lithotripsy (20 patients) were prospectively evaluated for renal functional and structural changes 60 days after the procedure and complete clearance of stones. Tc99-dimercaptosuccinic acid was used to assess cortical scarring and Tc99-diethylenetriamine pentaacetic acid and Tc99-levo levo ethylecysteine were used for glomerular filtration rate calculations, respectively. Results: The mean stone size was 24.4 mm and 13.7 mm in the percutaneous nephrolithotomy group and the shockwave lithotripsy group, respectively. No new cortical scars developed in either of the groups on Tc99-dimercaptosuccinic acid scan. Both the treated and untreated kidneys showed an overall insignificant fall in glomerular filtration rate in both the groups. The number of patients showing significant deterioration in the individual glomerular filtration rate in both the treated and untreated renal unit was more in the shockwave lithotripsy group. Conclusion: Both percutaneous nephrolithotomy and shockwave lithotripsy are comparable in terms of adverse effects on renal parenchyma and renal function. Level of evidence: Not applicable for this multicentre audit.

Síndrome de dolor lumbar agudo no traumático de origen renal: cólico renoureteral

The most frequent low back pain syndrome of renal origin is the renal-ureteral colic (RUC), secondary to ureteral lithiasis in 90% of cases. In emergency unit, proper management and the knowledge of complication criteria are mandatory. The pain in RUC and remaining acute renal pathologies is originated by the distention or irritation of the renal capsule. Regarding colic pain, it is caused by the release of vasodilators in response to offset the fall in glomerular filtration rate due to renal hypertension. Complication criteria are: fever, acute renal failure, incoercible pain (despite stepped analgesia) and urinoma. Diagnosis is clinical. If complication is suspected imaging tests are required. Analgesics of choice are nonsteroidal anti-inflammatory drugs. Urgent urinary diversion with ureteral catheter or percutaneous nephrostomy is a priority in complicated cases.

Changing Protein Permeability with Nephron Loss: Evidence for a Human Remnant Nephron Effect

Background: If loss of functioning nephrons predisposes to glomerular barotrauma (a “remnant nephron” effect), then glomerular permeability should increase as glomerular filtration rate (GFR) falls, as is observed in animal models of nephron loss. Methods: Changes in net renal protein permeability, defined as proteinuria or albuminuria per mL/min of GFR, were measured in the setting of nephron loss due to kidney donation (Assessing Long Term Outcomes in Living Kidney Donors cohort) or progressive chronic kidney disease (CKD; Modification of Diet in Renal Disease [MDRD], African American Study of Kidney Disease [AASK], and Chronic Renal insufficiency Cohort [CRIC] studies). Results: Following kidney donation, renal albumin permeability increased by 31% from predonation levels (p < 0.001). With progression of CKD, a 50% loss of residual GFR was accompanied by increases in proteinuria per mL/min GFR of 1.8-, 2.1-, and 1.6-fold in the MDRD, AASK, and CRIC cohorts, respectively (p < 0.001 for all), independent of changes in systolic blood pressure and ACEi/ARB use. A 70% reduction in GFR was associated with permeability increases of 3.1-, 4.4-, and 2.6-fold in the same cohorts. Among MDRD participants with progression of nonglomerular primary disease, the 75th percentile of final permeability was 141 mg/24 h proteinuria per mL/min GFR. This degree of permeability would have resulted in nephrotic range proteinuria had it been present at the baseline mean GFR of 40 mL/min, implying the development of de novo glomerular pathology as GFR fell. Increasing permeability also accompanied CKD progression in participants with nephrotic syndrome at baseline. Consequently, these participants had little improvement in 24 h proteinuria or serum albumin, despite substantial loss of functioning nephron mass across which the protein leak occurred. In the absence of a fall in GFR, there was no increase in permeability in any cohort. Conclusion: Nephron loss is accompanied by an increase in renal protein permeability, even in the absence of a primary glomerular disease. This is consistent with a remnant nephron effect in human CKD.

Global burden of late-stage chronic kidney disease resulting from dietary exposure to cadmium, 2015

Chronic exposures to cadmium (Cd) are associated with reduced glomerular filtration rate (GFR), increasing the risk of chronic kidney disease (CKD). In support of the World Health Organization (WHO)’s initiative to estimate the global burden of foodborne diseases, a risk assessment was performed to estimate the Disability-Adjusted Life Years (DALYs) due to late-stage CKD associated with dietary exposures to cadmium. Using the distribution of population GFRs, the prevalence of CKD was calculated as the proportion of humans whose GFR fall in the ranges corresponding to Stage 4 or Stage 5 CKD. The increase in the CKD prevalence due to cadmium exposure was simulated based on a previously reported pharmacokinetic model describing the relationship between dietary cadmium intake and urinary cadmium (UCd), as well as a previously published dose-response relationship between UCd and GFR. Cadmium-related incidence rate, calculated as the change in the prevalence during a one-year period, were used to compute the mortality and DALY in all WHO regions. It is estimated that dietary cadmium would result in a median of 12,224 stage 4 and stage 5 new CKD cases per year worldwide, resulting in 2064 global deaths and 70,513 DALYs. These data translate into a median global burden of 1.0 DALY per 100,000 population, which account for 0.2% of the global DALYs of CKD. While these results suggest that the overall impact of dietary cadmium exposure on global CKD is low, they do indicate that reasonable efforts to reduce dietary exposure will result a positive public health impact. This would be particularly the case in areas with elevated levels of dietary cadmium.

Fibroblast growth factor 23 and lipid metabolism association in chronic kidney disease

Recent scientificstudies have demonstrated the effect of fibroblast growth factor 23 (FGF-23) on the volume and distribution of body fat. The aim of our study was to investigate of lipid metabolism in patients with chronic kidney disease (CKD) and its relationship with FGF-23.&#x0D; Methods. We conducted a single-center, cohort retrospective study involved 106 patients with CKD 1-5 stages. Among the patients were 47 women (44%) and 59 men (56%) aged (49.6±13.9) years. All patients were determined the blood lipid spectrum: total cholesterol level (LDL), high density lipoproteins (HDL) and triglycerides (TG). The lipid profile was examined using a biochemical analyzer Cobas Integra 400 Plus. The C-terminal FGF-23 fragment was determined using a set of reagents for the enzyme immunoassay “Biomedica” (Astria). The glomerular filtration rate (GFR) was calculated using the CKD EPI formula (KDIGO 2012). All the statistical analyses were performed using Statistica 10.0.&#x0D; Results. In patients with CKD, progressive decrease in the level of total cholesterol, LDL cholesterol, HDL cholesterol and the increase in TG concurrent with the fall in GFR was detected (p&lt;0.001). The concentration of the C-terminal FGF-23 fragment progressively increased in parallel with the fall in GFR, reaching the highest values at CKD stage 5 (p&lt;0.001). A significant relationship was found between FGF-23 and total cholesterol (r =-0.45, p&lt;0.05), LDL (r=-0.29, p&lt;0.05), HDL (r=-0.54, p&lt;0.05), FGF-23 and TG (r=0.28, p&lt;0.05). Conclusions. CKD is characterized by a significant growth in TG levels, which increases with progression of renal dysfunction. The level of FGF-23 in CKD steadily increases in parallel with the decrease in GFR. The parameters of lipid metabolism, namely, total cholesterol, LDL, TG and HDL, have a reliable relationship with FGF-23 in CKD.

Sodium and Fluid Excretion With Torsemide in Healthy Subjects is Limited by the Short Duration of Diuretic Action.

BackgroundLoop diuretics are highly natriuretic but their short duration of action permits postdiuretic sodium retention, which limits salt loss unless dietary salt is severely restricted. We tested the hypothesis that a more prolonged duration of action would enhance salt loss.Methods and ResultsTen healthy participants were crossed over between 20 mg of oral immediate‐release or extended‐release (ER) torsemide while consuming a fixed diet with 300 mmol·d−1 of Na+. Compared with immediate‐release, plasma torsemide after ER was 59% lower at 1 to 3 hours but 97% higher at 8 to 10 hours as a result of a >3‐fold prolongation of time to maximal plasma concentrations. The relationship of natriuresis to log torsemide excretion showed marked hysteresis, but participants spent twice as long with effective concentrations of torsemide after ER, thereby enhancing diuretic efficiency. Compared with immediate‐release, ER torsemide did not reduce creatinine clearance and increased fluid (1634±385 versus 728±445 mL, P<0.02) and Na+ output (98±15 versus 42±17 mmol, P<0.05) despite an 18% reduction in exposure. Neither formulation increased K+ excretion.ConclusionsTorsemide ER prolongs urine drug levels, thereby increasing the time spent with effective drug concentrations, reduces postdiuretic Na+ retention, and moderates a fall in glomerular filtration rate. It caused significant Na+ loss even during very high salt intake. Thus, a short duration of action limits salt loss with loop diuretics. These conclusions warrant testing in subjects with edema and heart failure.

Lack of Impact of Hyperchloremia in Brain-Dead Organ Donors on the Onset of Kidney Allograft Function in the Recipients

BackgroundHyperchloremia produces renal vasoconstriction and fall in glomerular filtration rate. In 90% of brain-dead organ donors, diabetes insipidus develops, characterized by inappropriate diuresis, hyperosmolality, and hyperchloremia. The aim of this study was to determine the relationship between the serum concentration of chlorides of the donor and the onset of the function of the kidney allograft in the recipient. MethodsWe retrospectively studied 213 donors and kidney allograft recipients. Serum creatinine concentrations and glomerular filtration rates on the 1st, 7th, and 30th days after transplantation of the recipients from hyperchloremic donors were compared with the recipients from normochloremic donors, as well as the incidences of acute tubular necrosis and delayed graft function. ResultsOn the 1st day, serum creatinine concentrations of the recipients from hyperchloremic and normochloremic donors, respectively, were 448.2 ± 212.1 μmol/L and 502.2 ± 197.8 μmol/L (P = .1), on the 7th day, 168.6 ± 102.6 μmol/L and 196.9 ± 120.6 μmol/L (P = .13), and on the 30th day, 129.4 ± 43.3 μmol/L and 131.8 ± 43.6 μmol/L (P = .73). The differences were statistically significant. The groups also did not differ significantly in glomerular filtration rates and incidences of acute tubular necrosis and delayed graft function. ConclusionsIn this study, no significant correlation between serum chloride concentrations of the organ donors and the onset of the function of kidney allografts in the recipients was found.

Phosphodiesterase-5 inhibition preserves renal hemodynamics and function in mice with diabetic kidney disease by modulating miR-22 and BMP7

Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease. Preclinical and experimental studies show that PDE5 inhibitors (PDE5is) exert protective effects in DN improving perivascular inflammation. Using a mouse model of diabetic kidney injury we investigated the protective proprieties of PDE5is on renal hemodynamics and the molecular mechanisms involved. PDE5i treatment prevented the development of DN-related hypertension (P < 0.001), the increase of urine albumin creatinine ratio (P < 0.01), the fall in glomerular filtration rate (P < 0.001), and improved renal resistive index (P < 0.001) and kidney microcirculation. Moreover PDE5i attenuated the rise of nephropathy biomarkers, soluble urokinase-type plasminogen activator receptor, suPAR and neutrophil gelatinase-associated lipocalin, NGAL. In treated animals, blood vessel perfusion was improved and vascular leakage reduced, suggesting preserved renal endothelium integrity, as confirmed by higher capillary density, number of CD31+ cells and pericyte coverage. Analysis of the mechanisms involved revealed the induction of bone morphogenetic protein-7 (BMP7) expression, a critical regulator of angiogenesis and kidney homeostasis, through a PDE5i-dependent downregulation of miR-22. In conclusion PDE5i slows the progression of DN in mice, improving hemodynamic parameters and vessel integrity. Regulation of miR-22/BMP7, an unknown mechanism of PDE5is in nephrovascular protection, might represent a novel therapeutic option for treatment of diabetic complications.