eGFR In Chronic Kidney Disease Patients Research Articles

Evaluation of Thyroid Hormone, Fibroblast Growth Factor 23 and Cystatin C Concentrations in Patients with Chronic Kidney Disease

The age of 20-≤71years old. Also, in the current study, 30 healthy people were taken as a control group. Findings of the current study revealed substantial variations between chronic kidney disease (CKD) levels. The results of the current study demonstrated significant differences in s. urea between studied groups. Whereas, s. urea levels in CKD patients (107.42±8.52), were demonstrated a significant (P≤0.05) elevated in compared to a control (19.35± 2.16). while, creatinine levels in CKD patients (6.81± 0.55) demonstrated a significant (P≤0.05) elevated in compared to a control (0.84± 0.19). T3 levels in the end stage (5.17± 0.14) indicated a significant (P≤0.05) reduced than in other CDK stages and control group (6.34±0.28). T4 levels in the end stage (7.17±0.14) were significantly lower (P≤0.05) than in other CDK stages and control group (10.44±0.31). Thyroid-stimulating hormone (TSH) levels in the end stage (2.83±0.12) increased significantly (P≤0.05) compared to other CDK stages and control group (1.52±0.24). In contrast, fibroblast growth factor 23 (FGF-23) levels in the end stage (184.03±17.31) increased significantly (P≤0.05) as compared to other CDK stages and control group (5.16±0.45). Cystatin C level in CKD patients (17.11±1.94) was demonstrated a significant (P≤0.05) elevated in compared to a control (8.04±0.37). It is concluded from the study that CKD patients suffer from hypothyroidism based on hormone concentrations. The study also revealed a negative correlation between FGF-23 and Cystatin C levels with eGFR in CKD patients.

#2280 Kidney elastometry, X-flow algorithms to interrogate adult and pediatric number of nephrons

Abstract Background and Aims Standard ultrasound mainly provides information about structural changes in the kidney, whereas parenchymal Doppler ultrasound provides the renal resistance index (RI), which correlates with plasma creatinine levels. Unfortunately, in the case of isolated proteinuria and normal renal function/creatinine levels, these two classical approaches do not show any changes. Recent advances in ultrasound analysis, allowing the measure of kidney stiffness (sharewave elastometry) and the imaging of ultralow-flow vessels up glomeruli (such as X-Flow), might be helpful to identify kidney alterations in case of proteinuria with normal creatinine. We hypothesize that proteinuria with intact glomerular filtration may induce a measurable change in kidney stiffness and the size of low-flow microcircle, with different effects in acute and chronic conditions. We also verify whether the mismatch between creatinine, resistance index, and kidney size may suggest a specific nephrological disease. Method We conducted a transversal study on 301 patients with chronic kidney disease (CKD) and 160 kidney transplant patients (Tx), comparable for age, gender, and eGFR. For all patients, we retrieved the resistance indices of both the kidney and the spleen, clinical variables, shear wave elastrometry, and the X-Flow algorithm (Esaote) to detect the microcircle. We compared Conventional pulsed wave Doppler techniques (resistance index, RI) and ultrasensitive Doppler algorithm (Xflow, Esaote, Genoa, GE, Italy) to study the perfusion pattern and smaller angio-architecture of kidney's cortical vessels. X-Flow is a high-resolution and high-definition Doppler technology, which, with a new algorithm, makes better spatial resolution possible and maximizes Doppler signal penetration capabilities. We also identify a mismatch between creatinine and the renal RI, calculating the renal mismatch index (correlation between renal resistance index and creatinine level). The connection between the resistance index and the kidney size was tested as a significant marker of chronicity. Results The eGFR was best predicted by renal RI in Tx patients (Pearson −0.4, p < 0.01). At variance, the RI is a poor predictor of eGFR in CKD patients: in these subjects, the kidney longitudinal size was a better predictor of eGFR (Pearson's coefficient 0.39, p < 0.01). Using a large dataset from a previous study, we estimated the total number of nephrons using the following approximation: nephron number = (5270*total cortical volume – 61612)*number of kidneys. This formula is only valid for chronic patients and cannot be applied to polycystic patients. We speculated that while eGFR was proportional to the number of active glomeruli in CKD patients (thus correlating with kidney size), in TX patients, the local microcircle better explained the changes in eGFR. The consequence is that the eGFR has different meaning in CKD and Tx patients. Patients deviating from this pattern are identified as having an increased renal dissimilarity index. The multiple regression analysis revealed that RI also depended on age and cholesterol levels. The spleen resistance index correlated with cholesterol levels. The kidney mismatch index defined a subgroup of patients with tubular microcirculation abnormalities. Shearwave stiffness correlated with Resistance index (Pearson −0.3, p = 0.04) and, limited to Tx patients, to the cortical volume (Pearson = −0.446, p < 0.05) and number of nephrons (Pearson −0.44, p < 0.05), but was not associated with creatinine or eGFR. The extent of microcircle measured on X-flow images was altered in chronic forms of proteinuria with normal creatinine levels. Conclusion Kidney elastometry and kidney X-flow indices might show more sources of profitable information that can be collected from ultrasound approaches that allow the identification of a diseased kidney, even in the presence of regular architecture and average resistance index. The X-flow algorithm should be used to study the smaller vascular tree not visualizable with Doppler, such as the afferent arteriole.

#1375 Association of NT-proBNP and kidney function progression in chronic kidney disease patients without heart failure

Abstract Background and Aims Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is reported to be associated with higher risk of decline in kidney function. However, little evidence exists about the relationship between NT-proBNP and kidney function progression stratified by estimated glomerular filtration rate (eGFR) in chronic kidney disease (CKD) patients without heart failure. Therefore, we aim to investigate the association of NT-proBNP and CKD progression in different CKD stages for CKD patients without heart failure. Method A multicentric retrospective cohort study recruited 23860 patients diagnosed with CKD from China Renal Data System (CRDS) database. Eligible participants were classified into five groups according to eGFR. CKD progression was defined as a composite of an increase in serum creatinine ≥50% or a decrease in eGFR ≥40% from baseline or a need for kidney replacement therapy. A linear regression model evaluated the relationship between eGFR and NT-proBNP. Cox regression analysis assessed the association between NT-proBNP and CKD progression. We also performed restricted cubic spline (RCS) and threshold effect analysis to investigate non-linear relationships between NT-proBNP and CKD progression. Results In a linear regression model, NT-proBNP was negatively correlated with eGFR in CKD patients. Each decrease of 15 ml/min/1.73 m2 in eGFR was associated with 1.06-fold, 1.50-fold, 1.52-fold, 1.94-fold, 3.37-fold higher levels of log (NT-proBNP) in CKD patients with stage 1-2, 3a, 3b, 4 and 5 respectively. In the multivariable Cox hazard model, elevated NT-proBNP was associated with a greater risk of kidney function progression, particularly among CKD stage 3 patients (stage 3a: HR, 1.42, 95% CI, 1.32-1.53; stage 3b: HR, 1.43, 95% CI, 1.32-1.54), with P-interaction≤0.001. However, the correlation of NT-proBNP and CKD progression had no statistical significance among CKD patients with stages 4-5 after sensitivity analyses. RCS and two-segment Cox regression model showed reversed L-shaped non-linear relationships between NT-proBNP and CKD progression in CKD patients with stages 1-4, with the inflection point at 250 pg/mL, 750 pg/mL, 653 pg/mL, 526 pg/mL, but not in stage 5 (Figure). Conclusion NT-proBNP may be a reliable biomarker to predict CKD progression in stages 1-3 CKD (mainly for stage 3) without heart failure. This helps clinicians predict a decline in kidney function early and set the threshold for therapy. However, the predictive role of NT-proBNP in in advanced CKD patients is insignificant.

A new approach for cognitive impairment pattern in chronic kidney disease.

Chronic kidney disease (CKD) is associated with an elevated risk of neurocognitive disorders (NCDs). It remains unclear whether CKD-related NCDs have a specific cognitive pattern or are earlier-onset phenotypes of the main NCDs (vascular NCDs and Alzheimer's disease). We used the Mini Mental State Examination score (MMSE) to assess cognitive patterns in 3003 CKD patients (stage 3-4) followed up over 5 years in the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort. After normalizing MMSE scores to a 0-to-100 scale, the associations between the baseline estimated glomerular filtration rate (eGFR, using the Chronic Kidney Disease Epidemiology Collaboration creatinine formula) and changes in each MMSE domain score were assessed in linear mixed models. Patients (age: 67±13years old; males: 65%, mean eGFR: 33± 12mL/min/1.73m2) had a good baseline cognitive functions: the mean MMSE score was 26.9/30±2.9. After adjustment for age, sex, educational level, depression (past or present), cardiovascular risk factors and cerebrovascular disease, a lower baseline eGFR (per 10mL/min/1.73m2) was associated with a 0.53-point decrement [P<.001; 95% confidence interval (CI) (-0.98, -0.08)] for orientation, a 1.04-point decrement [P=.03; 95% CI (-1.96, -0.13)] for attention and calculation, a 0.78-point decrement [P=.003; 95% CI (-1.30, -0.27)] for language, and a 0.94-point decrement [P=.02; 95% CI (-1.75, -0.13)] for praxis. Baseline eGFR was not, however, associated with significant changes over time in MMSE domain scores. A lower eGFR in CKD patients was associated with early impairments in certain cognitive domains: praxis, language and attention domains before an obvious cognitive decline. Early detection of NCD in CKD patients must be performed before clinically cognitive decline using preferably tests assessing executive, attentional functions and language, rather than memory tests. This early cognitive screening could lead to a better management of cognitive impairment and their consequences on CKD management.

Correlation between estimated glomerular filtration rate and serum electrolytes in chronic kidney disease patients

Background: The occurrence of chronic kidney disease (CKD) a highly prevalent condition has been escalating in recent years. Electrolytes are the key to homeostasis and furthermore, their regulation is dependent upon renal function. CKD is associated with aberrations in the metabolism of electrolytes such as calcium, magnesium, sodium, and potassium. Aims and Objectives: The aim of this study is to study the correlation between estimated glomerular filtration rate (eGFR) and serum electrolytes in CKD patients. Materials and Methods: The present study was a cross-sectional study. One hundred patients with CKD aged 18 years or above were enrolled with inclusion and exclusion criteria. Complete blood investigations, urine analysis and ultrasonographic findings for detection of CKD were done and a semi-structured pro forma was used to record clinical profile in a cross-sectional study and patients were grouped into their respective CKD stages based on their eGFR. Results: The mean value of eGFR was 40.92±21.35 mL/min/1.73 m2. The mean value of serum sodium, calcium, magnesium, and potassium was 137.1±2.16 meq/L, 9.15±0.61 mg/dL, 3.16±0.93 mg/dL, and 4.65±0.96 meq/L, respectively. In the present study, we found that the mean serum magnesium levels in Stages 1, 2, 3, 4, and 5 of CKD were 2.10±0.20, 2.10±0.28, 2.74±0.50, 3.95±0.54, and 4.66±0.43 mg/dL, respectively. Mean serum magnesium levels were the mean serum potassium levels in Stages 1, 2, 3, 4, and 5 of CKD were 4.13±0.57, 4.15±0.68, 3.86±0.41, 5.55±0.39, and 6.25±0.08 meq/L, respectively. The mean serum calcium levels in Stages 1, 2, 3, 4, and 5 of CKD were 9.83±0.05, 9.79±0.20, 9.43±0.27, 8.72±0.38, and 7.8±0.10 mg/dL, respectively. The mean serum sodium levels in Stages 1, 2, 3, 4, and 5 of CKD were 137.33±0.57, 136.43±2.87, 136.92±2.15, 137.51±1.90, and 137.5±2.07 meq/L, respectively. Conclusion: There was significant rise in serum potassium and magnesium levels with decrease in eGFR in CKD patients. There was significant fall in serum calcium levels with decrease in eGFR in CKD patients. There was no significant correlation between serum sodium levels and eGFR in CKD patients.

Effect of dapagliflozin on the initial estimated glomerular filtration rate dip in chronic kidney disease patients without diabetes mellitus

BackgroundDapagliflozin (DAPA), a sodium-glucose transporter 2 inhibitor (SGLT2i), attenuates kidney outcomes in patients with not only diabetes mellitus (DM) but also chronic kidney disease (CKD). SGLT2i-derived initial dip in estimated glomerular filtration rate (eGFR) has been considered to reduce excess glomerular pressure, followed by renal protection in patients with DM. However, whether DAPA confers the eGFR dip and its independent determinants for CKD patients without DM are unclear.MethodsA total of 126 patients with CKD treated with 10 mg DAPA daily was retrospectively registered. After participants with missing data and DM were excluded, 51 participants were enrolled.ResultsAn initial eGFR dip was observed 1 month after initiation of DAPA, which was sustained until 2 months. DAPA did not affect urinary protein excretion; however, serum uric acid was decreased, while hemoglobin level was increased. Multiple regression analysis revealed that eGFR at baseline was the only independent determinant of the initial dip of eGFR. The patients currently showing exacerbation of glomerular hyperfiltration exhibited the larger initial eGFR dip rather than those showing progressive renal dysfunction. The patients meeting exclusion criteria of DAPA-CKD trial exhibited same degree of the initial eGFR dip as others.ConclusionsDAPA causes an initial dip of eGFR in CKD patients without DM at 1 month after starting DAPA treatment. A higher eGFR at baseline predicts a large initial eGFR dip, which might be linked to the subsequent recovery in eGFR in CKD patients without DM.

Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients.

IntroductionChronic kidney disease (CKD) has been recognized as a global health problem. Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR).Material and methodsThis was a case-control study consisting of 90 subjects. Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. Serum α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation.ResultsSerum α-Klotho (ng/ml) was found to be 2.59±0.98 in cases as compared to 0.24±0.09 in controls (p< 0.01). The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. (p< 0.01). Serum Klotho has a negative correlation with eGFR in CKD patients (r = -0.065; p = 0.648).ConclusionThe serum α-Klotho level was significantly higher in CKD patients than in healthy volunteers. Both serum α-Klotho and oxidative stress were negatively correlated with eGFR in CKD patients. Serum α-Klotho can be a suitable biomarker in CKD patients with declining GFR.

An Innovative Ultrasound Technique for Early Detection of Kidney Dysfunction: Superb Microvascular Imaging as a Reference Standard.

Background: Superb microvascular imaging (SMI) is an innovative ultrasound image processing technique that provides greater detail and better visualization of small branching vessels. We assume that SMI will provide sufficient information regarding the severity of chronic kidney disease (CKD) and reflecting histological changes. Aims: The aims was to assess the capabilities of SMI imaging regarding the early detection of kidney dysfunction and renal fibrosis in comparison to the reference standard renal biopsy for the early diagnosis of kidney fibrosis. Methods: SMI was performed in patients (n = 52) with CKD stage 2–5, where some of them underwent biopsy proven CKD and fibrosis as part of the diagnosis. In addition, biochemical tests were performed, including kidney function tests, urine collection for proteinuria, and the estimation of GFR by MDRD or CKD-EPI eGFR in CKD patients and healthy controls (n = 17). All subjects underwent SMI, where vascularity is expressed as the SMI index (a low index reflects low vascularity/fibrosis and vice versa). Results: The SMI vascular index was significantly lower in CKD patients as compared with healthy controls (72.2 ± 12.9 vs. 49.9 ± 16.7%, p < 0.01). Notably, a moderate correlation between the SMI index and eGFR was found among the CKD patients (r = 0.56, p < 0.001). Similarly, a strong correlation was found between SCr and the SMI index of the diseased subjects (r = −0.54, p < 0.001). In patients who underwent renal biopsy, the SMI index corresponded with the histological alterations and CKD staging. Conclusions: This study demonstrated that SMI imaging may be utilized in CKD patients of various stages for the evaluation of chronic renal morphological changes and for differentiation between CKD grades.

Effects of non-surgical periodontal therapy on serum inflammatory factor high-sensitive C-reactive protein, periodontal parameters and renal biomarkers in patients with chronic periodontitis and chronic kidney disease.

Chronic kidney disease (CKD) is associated with significant morbidity and mortality, and there are various risk factors for this disease. Although the association between CKD and periodontal disease (PD) has been reported in various cross-sectional studies, longitudinal intervention studies are scarce. This study aimed to evaluate the effects of non-surgical periodontal therapy (NSPT) on periodontal clinical parameters, serum inflammatory factor high-sensitivity C-reactive protein (hs-CRP) and renal biomarkers in patients with CKD and chronic periodontitis (CP). A total of 80 patients with confirmed CKD aged 22-65 years, attending the Institute of Kidney Diseases Research Centre (IKDRC) in Ahmedabad, India, and referred to the Government Dental College and Hospital, Ahmedabad (GDCHA), were enrolled in this study. The patients were divided into 2 groups: group 1 received NSPT, including scaling and root planing (SRP), as well as oral hygiene instructions; and group 2 received oral hygiene instructions without NSPT. Periodontal clinical parameters, such as probing pocket depth (PPD), clinical attachment loss (CAL), bleeding on probing (BoP), the periodontal inflamed surface area (PISA) score, and the Simplified Oral Hygiene Index (OHI-S), were recorded. Biomarkers, including hs-CRP, the estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR), were obtained from medical records. The comparisons of periodontal parameters, hs‑CRP and renal biomarkers within and between the groups were performed at baseline, and 3 and 6 months after treatment. The periodontal parameter scores as well as the serum levels of hs‑CRP and UACR significantly decreased while eGFR significantly increased in group 1 after treatment as compared to baseline (p < 0.001). Six months after treatment, group 1 showed significantly lower values than group 2 for periodontal parameters, the serum levels of hs‑CRP and renal biomarkers except for eGFR, which improved and increased (p < 0.001). Periodontitis is an important source of chronic inflammation and the treatment of periodontitis can hinder systemic inflammation in CKD patients. Non-surgical periodontal therapy resulted in improved periodontal health, with significant decreases in hs‑CRP and UACR, and an increase in eGFR in CKD patients with CP in comparison with CKD patients not receiving NSPT.

Effect of CPAP Therapy on Kidney Function in Patients With Chronic Kidney Disease: A Pilot Randomized Controlled Trial

OSA is common in chronic kidney disease (CKD) and may accelerate a decline in kidney function. It is not clear whether treatment of OSA with CPAP improves kidney function. Does treatment with CPAP improve kidney function in patients with CKD and coexisting OSA? A randomized, controlled, nonblinded, parallel clinical trial was performed of patients with stages 3 and 4 CKD and coexisting OSA comparing the effect of CPAP vsusual care on the estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (ACR) over 12months. Fifty-seven patients were enrolled and 30 were randomized to CPAP. They had moderately severe CKD (eGFR, 38.4 ± 1.5mL/min/1.73 m2) and significant OSA and nocturnal hypoxemia (oxygen desaturation index: 23.9 events/h; interquartile range [IQR], 20.3 events/h; mean peripheral capillary oxygen saturation: 89.5%; IQR, 1.7%); 60%had baseline albuminuria (ACR, > 3mg/mmol). No significant difference was found between CPAP and usual care in the change in eGFR and ACR over 12months. Although some improvement in eGFR occurred with CPAP therapy in patients with a lower risk of CKD progression, this did not reach statistical significance. Although CPAP did not provide additional renal benefits over usual care in all CKD patients, some evidence suggested that CPAP slowed the decline in eGFR in CKD patients with a lower risk of CKD progression. These preliminary data support the need for larger clinical trials exploring the effects of CPAP on kidney function. ClinicalTrials.gov; No.: NCT02420184; URL: www.clinicaltrials.gov.

The Difference in the Changes of Indoxyl Sulfate after Catheter Ablation among Atrial Fibrillation Patients with and without Kidney Dysfunction

Indoxyl sulfate (IS), a protein-bound uremic toxin, induces chronic kidney disease (CKD) and atrial fibrillation (AF). Catheter ablation (CA) of AF improves the renal function. However, the transition of uremic toxins is unclear. This study aimed to investigate the transition of the serum IS level in AF patients with and without CKD after CA. A total of 138 consecutive AF patients who underwent CA and maintained sinus rhythm were prospectively enrolled (paroxysmal AF 67.4%). The patients were divided into 4 groups (non-CKD/low-IS:68, non-CKD/high-IS:28, CKD/low-IS:13, and CKD/high-IS:29). The plasma IS levels and estimated glomerular filtration rate (eGFR) were determined before and 1-year after CA. CKD was defined as CKD stage III and a high-IS according to the mean IS (IS ≥ 1.1 μg/ml). CA significantly improved the eGFR in CKD patients (p < 0.001). The serum IS level in the non-CKD/high-IS group was significantly decreased (from 1.7 ± 0.7 to 1.1 ± 0.6 μg/ml, p < 0.001). However, the serum IS level in the CKD/high-IS group did not improve (from 1.9 ± 0.9 to 1.7 ± 0.7 μg/ml, p = 0.22). The change in the IS in the CKD patients significantly differed from that in those without CKD. In the CKD patients, CA did not significantly decrease the IS, a risk factor of CKD, regardless of an improved eGFR.

Effect of biologic drugs on renal function in psoriasis patients with chronic kidney disease

To the Editor: Patients with psoriasis are at an increased risk of chronic kidney disease (CKD) and end-stage renal disease, which may lead to higher risk of death.1 CKD can worsen over time, and patients with progressive decline in estimated glomerular filtration rate (eGFR) and proteinuria are at a higher risk for progression to end-stage renal disease.2 The estimated decline in eGFR in CKD patients is 2.83 and 1.66 mL/min/1.73 m2 per year (8.8% ± 12.9%) in men and women, respectively, and an increased rate of decline is associated with male sex, proteinuria, and high systolic blood pressure.

Role of febuxostat in retarding progression of diabetic kidney disease with asymptomatic hyperuricemia: A 6-months open-label, randomized controlled trial.

Introduction: Hyperuricemia is associated with chronic kidney disease (CKD) progression and poor cardiovascular outcomes. We studied the effect of febuxostat on estimated glomerular filtration rate (eGFR), proteinuria and monitored the safety profile of the medication.Material and Methods: This is a prospective open-label, randomized study in CKD stage 3 and 4 patients with diabetic nephropathy and asymptomatic hyperuricemia. Patients were randomized into febuxostat 40 mg daily and no treatment group using block randomization method and were followed up for 6 months. Their usual care for diabetes mellitus, hypertension and dyslipidemia were continued in the study. Blood and urine investigations were monitored at baseline, 3 months and 6 months.Results: The eGFR in febuxostat group was stabilized at 6 months with no significant reduction [26.2 (IQR 14.30) at baseline to 26.3 (IQR 15.2) ml/min/1.73 m2]. Whereas, there was a significant reduction of the eGFR in no treatment group from 28.2 (IQR 17.9) to 27.6 (IQR 19.3) ml/min/1.73 m2 (p value < 0.01). We found the HbA1c (glycosylated hemoglobin) was significantly increased in febuxostat group from 7.2 ± 0.5 % at baseline to 7.6 ± 1.4 at 6 months (p value 0.04) but no significant change of HbA1c in the no treatment group. Proteinuria level was unchanged in both groups. The commonest adverse event was joint pain.Conclusions: Febuxostat was able to preserve eGFR in CKD patients with diabetic nephropathy and this effect was beyond glycemic control. Increment of HbA1c level in febuxostat group needs further larger trials.

Thyroid hormone replacement therapy for primary hypothyroidism leads to significant improvement of renal function in chronic kidney disease patients

The interactions between kidney and thyroid functions have been known for many years; however, there are few studies on the extent of the improvements and long-term changes of renal function after thyroid hormone replacement therapy (THRT) in chronic kidney disease (CKD) patients. The purpose of this study was to determine how THRT affects the estimated glomerular filtration rate (eGFR) in CKD patients with primary hypothyroidism. A retrospective investigation was performed on 51 Japanese patients (15 men and 36 women) with primary hypothyroidism. The changes in eGFR after THRT were examined according to the existence of CKD and severity of thyroid function. eGFR increased rapidly over the first 6 months after THRT in CKD patents, which was followed by a plateau. There was a correlation between eGFR and the severity of hypothyroidism, which was independent of age, and eGFR in severely hypothyroid patients significantly increased up to levels that were similar to mildly hypothyroid patients after THRT. eGFR improved more in the lower initial eGFR group and increased about 30 % in CKD patients (47.5 ± 7.7 vs. 62.1 ± 9.5 ml/min/1.73 m(2), P < 0.01). Moreover, eGFR in CKD patients with mild to moderate hypothyroidism was significantly increased compared to that in non-CKD patients. Our data suggested that hypothyroidism contributed to the reduction in eGFR, especially in CKD patients; therefore, patients with CKD should positively be examined for thyroid function, and appropriate THRT should be started if needed.

Hepcidin and disordered mineral metabolism in chronic kidney disease

Hepcidin regulates iron homeostasis by blocking iron absorption from the gut and iron release from macrophage and hepatocyte stores. Hepcidin levels are elevated in kidney failure and thus, are thought to contribute to dysregulation of iron homeostasis in chronic kidney disease (CKD). However, the primary factors associated with increased hepcidin levels in CKD patients have not been well-defined. In particular, few studies examined the relationships between hepcidin and disorders of mineral metabolism, which are among the earliest and most common complications of CKD. We examined the associations between hepcidin, iron indexes, and markers of mineral metabolism in 125 patients from across the spectrum of pre-dialysis CKD. Bioactive hepcidin levels were measured in serum samples by competitive ELISA. Hepcidin was inversely associated with eGFR and linearly associated with ferritin (p < 0.001 for both). In unadjusted analyses, increased serum phosphate and parathyroid hormone (PTH) and decreased 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were associated with increased hepcidin. When examined in forward stepwise regression analysis, higher phosphate and PTH levels and lower 1,25(OH)2D and FGF23 levels were selected as independent predictors of higher hepcidin levels, whereas there was no association between eGFR and hepcidin. Abnormalities in phosphate and vitamin D metabolism were associated with increased hepcidin levels independently of eGFR in CKD patients. These findings suggest that disorders of mineral metabolism may promote increased hepcidin secretion in CKD. Whether inflammation mediates these associations requires further study.