Anemia and vitamin D deficiency are both important health issues; however, the nature of the association between vitamin D and either hemoglobin or anemia remains unresolved in the general population.
Data on 11,206 adults were obtained from the fifth Korean National Health and Nutritional Examination Survey. A generalized additive model was used to examine the threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and hemoglobin levels. A multivariate logistic regression for anemia was conducted according to 25(OH)D quintiles. All analyses were stratified according to sex and menstrual status.
The generalized additive model confirmed a threshold 25(OH)D level of 26.4 ng/mL (male, 27.4 ng/mL; premenopausal females, 11.8 ng/mL; postmenopausal females, 13.4 ng/mL). The threshold level affected the pattern of association between 25(OH)D and anemia risk: the odds ratio of the 1st quintile but not the 2nd, 3rd, and 4th quintiles were significantly different from the 5th quintile in both premenopausal and postmenopausal females, however there was no obvious trend in males.
This population-based study demonstrated a non-linear relationship with a threshold effect between serum 25(OH)D and hemoglobin levels in females. Further interventional studies are warranted to determine whether the appropriate level of hemoglobin can be achieved by the correction of vitamin D deficiency.
Elevated blood pressure (BP) is the most common cause of cardiovascular disease. Salt intake has a strong influence on BP, and plasma sodium (pNa) is increased with progressive increases in salt intake. However, the associations with pNa and BP had been reported inconsistently. We evaluated the association between pNa and BP, and estimated the risks of all-cause-mortality according to pNa levels. On the basis of data collected from health checkups during 1995-2009, 97,009 adult subjects were included. Positive correlations between pNa and systolic BP, diastolic BP, and pulse pressure (PP) were noted in participants with pNa ≥138 mM/L (P<0.001). In participants aged ≥50 yr, SBP, DBP, and PP were positively associated with pNa. In participants with metabolic syndrome components, the differences in SBP and DBP according to pNa were greater (P<0.001). A cumulative incidence of mortality was increased with increasing pNa in women aged ≥50 yr during the median 4.2-yr-follow-up (P<0.001). In women, unadjusted risks for mortality were increased according to sodium levels. After adjustment, pNa ≥145 mM/L was related to mortality. The positive correlation between pNa and BP is stronger in older subjects, women, and subjects with metabolic syndrome components. The incidence and adjusted risks of mortality increase with increasing pNa in women aged ≥50 yr.
Age; Blood Pressure; Mortality; Plasma Sodium; Sex Characteristics
The addition of relevant parameters to acute kidney injury (AKI) criteria might allow better prediction of patient mortality than AKI criteria alone. Here, we evaluated whether inclusion of AKI duration could address this issue.
AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines in 2,143 critically ill patients, within 15 days of patient admission. AKI cases were categorized according to tertiles of AKI duration: 1st tertile, 1–2 days; 2nd tertile, 3–5 days; and 3rd tertile, ≥6 days. The hazard ratios (HRs) for overall survival rates in three groups were calculated after adjustment for multiple covariates compared with ICU patients without AKI as the reference group. The predictive ability for mortality was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curve.
AKI increased the HRs for overall mortality, and the mortality rate increased with AKI duration: the adjusted HRs were 1.99 (1st tertile), 2.67 (2nd tertile), and 2.85 (3rd tertile) compared with the non-AKI group (all Ps < 0.001). The AUC of the ROC curve for overall mortality based on the AKI duration groups (0.716) was higher than the AUC of AKI staging using the KDIGO guidelines (0.696) (P = 0.001). When considering KDIGO stage and AKI duration together, the AUC (0.717) was also significantly higher than that using the KDIGO stage alone (P < 0.001).
AKI duration is an additional parameter for the prediction of mortality in critically ill patients. The inclusion of AKI duration could be considered as a refinement of the AKI criteria.
Acute kidney injury; Acute renal failure; Duration; Mortality; Survival
Bilirubin (BIL) has been recognized as an endogenous antioxidant that shows a protective effect for cardiorenal diseases. We investigated whether administration of BIL had a protective effect on cyclosporine (CsA)-induced nephropathy (CIN), and examined the effects of BIL on the oxidative stress and apoptosis.
BIL was pretreated intraperitoneally three times for a week (60 mg/kg), and CsA was injected for 4 weeks (15 mg/kg/day, subcutaneous). Proximal tubular epithelial (HK2) cells were pretreated with 0.1mg/ml of BIL for 24 hours, and then treated with 20 μM of CsA for another 24 hours.
CsA induced marked increases in urine kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) concentrations (P < 0.05). BIL reduced urine Kim-1 in CIN (P < 0.05), while urine NGAL exhibited a decreasing tendency. In CsA-treated rat kidneys, the protein expression of NOX4 and p22phox was reduced by BIL (P < 0.05). BIL ameliorated CsA-induced arteriolopathy, tubulointerstitial fibrosis, tubular injury, and the apoptosis examined by TUNEL assay (P < 0.01). In HK2 cells, BIL reduced intracellular reactive oxygen species in CsA-treated cells. CsA increased the protein expression of bax, cleaved caspase-9, caspase-3 and the activity of caspase-3; however, the anti-apoptotic bcl-2 protein was reduced. These changes were recovered by BIL (P < 0.05).
The direct administration of BIL protected against CsA-induced tubular injury via inhibition of oxidative stress and apoptosis.
Apoptosis; Bilirubin; Cyclosporine; Oxidative stress; Renal injury
Warfarin-related nephropathy (WRN) is a recently described disease entity, in which excessive warfarinization (international normalized ratio (INR) >3.0) causes acute kidney injury. Previous reports regarding WRN included few Asian patients who might have differed from the western WRN patients in terms of genetic and environmental factors.
During the period of March 2003 to December 2011, the data about a total of 1297 patients who had serum creatinine (sCr) level measured within 1 week after INR >3.0 and within 6 months before INR >3.0 was analyzed through the retrospective review of electronic medical records of a single tertiary hospital in Korea.
WRN developed in 19.3% of patients having excessive warfarinization. The incidence was higher in the chronic kidney disease (CKD) group than the non-CKD group. The risk of WRN increased as the basal serum albumin level decreased and was strongly associated with highest quartile serum AST level at post INR elevation and the presence of congestive heart failure. But the presence of atrial fibrillation was protective against the development of WRN. Neither the presence of CKD nor basal estimated glomerular filtration rate (eGFR) was an independent risk factor for WRN. Despite no difference in the basal sCr level, the sCr level was higher in patients with WRN than those without WRN after follow-up. The mortality rates were also higher in patients with WRN.
WRN developed in 19.3% of patients having excessive warfarinization. A lower basal serum albumin, highest quartile serum AST level at post INR elevation, and congestive heart failure were associated with the occurrence of WRN. The development of WRN adversely affected renal and patient outcomes.
Lower potassium intake is considered to be correlated with diabetes incidence. However, few studies have investigated the effect of potassium intake on metabolic syndrome (MetS). Data was taken from the Korean National Health and Nutritional Examination Survey (2008–2010) using weighted adjustment. MetS was defined as per the revised National Cholesterol Education Program criteria. Homeostasis model assessment indices were calculated to diagnosis insulin resistance (IR). A total of 16,637 participants (44±0.25 years) were included. Women ingested lower amounts of potassium (2.71±0.02 g/day) than men (3.45±0.03 g/day). A curvilinear association between potassium intake and MetS prevalence was found among women. Women with less than the Adequate Intake (4.7 g/day) of potassium had an 11% risk reduction for MetS (adjusted odds ratio [OR], 0.89; 95% confidence interval [CI], 0.82–0.96; P = 0.004) and a 10% risk reduction for IR (OR, 0.90; 95% CI, 0.82–0.99; P = 0.026) for every 1 g/day potassium increase. Compared with the reference group (3.5–4.5 g/day), potassium intake was inversely associated with an increased risk of MetS (1.5–2.5 g/day; OR, 1.29; 95% CI, 1.02–1.63; P = 0.035; <1.5 g/day; OR, 1.40; 95% CI, 1.06–1.85; P = 0.017) and IR (<1.5 g/day; OR, 1.36; 95% CI, 1.05–1.76; P = 0.021). This relationship was more prominent in postmenopausal women, but not observed among men. Higher potassium intake is significantly associated with a lower MetS prevalence in women, and IR is believed to be connected.
Gentamicin nephrotoxicity is one of the most common causes of acute kidney injury (AKI). Hypoxia-inducible factor (HIF) is effective in protecting the kidney from ischemic and toxic injury. Increased expression of HIF-1α mRNA has been reported in rats with gentamicin-induced renal injury. We hypothesizd that we could study the role of HIF in gentamicin-induced AKI by modulating HIF activity. In this study, we investigated whether HIF activation had protective effects on gentamicin-induced renal tubule cell injury. Gentamicin-induced AKI was established in male Sprague-Dawley rats. Cobalt was continuously infused into the rats to activate HIF. HK-2 cells were pre-treated with cobalt or dimethyloxalylglycine (DMOG) to activate HIF and were then exposed to gentamicin. Cobalt or DMOG significantly increased HIF-1α expression in rat kidneys and HK-2 cells. In HK-2 cells, HIF inhibited gentamicin-induced reactive oxygen species (ROS) formation. HIF also protected these cells from apoptosis by reducing caspase-3 activity and the amount of cleaved caspase-3, and -9 proteins. Increased expression of HIF-1α reduced the number of gentamicin-induced apoptotic cells in rat kidneys and HK-2 cells. HIF activation improved the creatinine clearance and proteinuria in gentamicin-induced AKI. HIF activation also ameliorated the extent of histologic injury and reduced macrophage infiltration into the tubulointerstitium. In gentamicin-induced AKI, the activation of HIF by cobalt or DMOG attenuated renal dysfunction, proteinuria, and structural damage through a reduction of oxidative stress, inflammation, and apoptosis in renal tubular epithelial cells.
The timing for dialysis initiationis still debated. The aim of this study was to compare mortality rates, using a propensity-score approach, in dialysis patients with early or late starts. From January 2000 to June 2009, incident adult patients (n = 836) starting dialysis for end-stage renal disease (ESRD) were enrolled. The patients were assigned to either an early- or late-start group depending on the initiation time of the dialysis. After propensity-score-basedmatching, 450 patients remained. At the initiation of dialysis, the mean estimated glomerular filtration rate (eGFR) was 11.1 mL/min/1.73 m2 in the early-start group compared with 6.1 mL/min/1.73 m2 in the late-start group. There were no significant differences in survival between the patients in the early- and late-start groups (Log rank tests P = 0.172). A higher overall mortality risk was observed in the early-start group than in the late-start group for the patients aged ≥ 70 yr (hazard ratio [HR]: 3.29; P = 0.048) and/or who had albumin levels ≥ 3.5 g/dL (HR: 2.53; P = 0.046). The survival of the ESRD patients was comparable between the patients in the early and late-start groups. The time to initiate dialysis should be determined based on clinical findings as well as the eGFR.
End Stage Renal Disease; Glomerular Filtration Rate; Renal Dialysis; Mortality; Peritoneal Dialysis
Coronary artery calcification (CAC) has been described in individuals with chronic kidney disease (CKD), and its presence is associated with an increased risk of cardiovascular death. However, it is unclear whether there is an independent relationship between renal function and CAC. Therefore, we evaluated the association between renal function and CAC.
Materials and Methods
We retrospectively reviewed 870 Korean patients who had undergone computed tomographic coronary angiography. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease study formula with an ethnic factor for the Korean population. The CKD stages were classified using estimated GFR (eGFR) and proteinuria.
The mean age of the participants was 56.8±11.8 years, and the mean eGFR was 89.4±16.5 mL/min/1.73 m2. Hypertension and diabetes were noted in 41.5 and 17.0% of patients, respectively. There were 584 and 286 patients with no CAC and with CAC, respectively. After adjusting for confounding variables, late stage CKD was associated with CAC [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.05-7.46]. However, early stage CKD was not associated with CAC (OR 1.61, 95% CI 0.92-2.82). Diabetes was an independent risk factor of CAC (OR 2.06, 95% CI 1.36-3.13). There was no significant association between proteinuria and CAC (OR 1.65, 95% CI 0.96-2.85).
CAC is related to late stage CKD in nondialyzed patients. These findings emphasize that individuals with CAC should be considered a high-risk population for decreased renal function.
Chronic kidney disease; coronary artery calcification; proteinuria; renal function
Only a few large-scale studies have investigated the association between health-related quality of life (HRQOL) and renal function. Moreover, the HRQOL of patients with moderate renal dysfunction is frequently underestimated by healthcare providers. This study assessed the impact of renal function on preference-based HRQOL in Korean adult population.
We analyzed data for 5,555 adults from the 3rd Korean National Health and Nutritional Examination Survey 2005. The EuroQol-5D (EQ-5D) utility score was used to evaluate HRQOL. The study subjects were stratified into three groups based on their estimated glomerular filtration rates (eGFRs): ≥ 90.0, 60.0-89.9 and 30.0-59.9 mL/min/1.73 m2. Individuals with advanced renal dysfunction were excluded from the analysis.
The proportions of participants who reported problems in each of the five EQ-5D dimensions increased significantly with decreasing eGFR. However, a significant decrease in the EQ-5D utility score was observed among participants with an eGFR of 30.0-59.9 mL/min/1.73 m2. Participants with an eGFR of 30.0-59.9 mL/min/1.73 m2 had an almost 1.5-fold higher risk of impaired health utility (the lowest quartile of EQ-5D utility score) compared with those participants with eGFRs ≥ 90.0 mL/min/1.73 m2, after adjustment for age, gender, health-related behaviors, socioeconomic and psychological variables, and other comorbidities. Among the five dimensions of the EQ-5D, an eGFR of 30.0-59.9 mL/min/1.73 m2 was an independent determinant of self-reported problems in the mobility and pain/discomfort dimensions.
Although age affects the association between renal dysfunction and the EQ-5D, moderate renal dysfunction seems to be an important determinant of impaired health utility in a general population and may affect the mobility and pain/discomfort dimensions of health utility.
Chronic kidney disease; EuroQol-5D; Preference-based health utility
Malnutrition and inflammation are related to high rates of morbidity and mortality in hemodialysis patients. Resistin is associated with nutrition and inflammation. We attempted to determine whether resistin levels may predict clinical outcomes in hemodialysis patients. We conducted a prospective evaluation of 100 outpatients on hemodialysis in a single dialysis center (male, 46%; mean age, 53.7 ± 16.4 yr). We stratified the patients into 4 groups according to quartiles of serum resistin levels. During the 18-month observational period, patients with the lowest quartile of serum resistin levels had poor hospitalization-free survival (log rank test, P = 0.016). After adjustment of all co-variables, patients with the lowest quartile of serum resistin levels had poor hospitalization-free survival, compared with reference resistin levels. Higher levels of interleukin-6 were an independent predictor of poor hospitalization-free survival. In contrast, serum resistin levels were not correlated with interleukin-6 levels. The current data showed that low resistin levels may independently predict poor hospitalization free survival in hemodialysis patients.
Renal Dialysis; Resistin; Hospitalization
Accurate measurement of the volume status in hemodialysis patients is important as it can affect mortality. However, no studies have been conducted regarding volume management in cases where a sudden change of body fluid occurs, such as during puerperium in hemodialysis patients. This report presents a case in which the patient was monitored for her body composition and her volume status was controlled using a body composition monitor (BCM) during the puerperal period. This case suggests that using a BCM for volume management may help maintain hemodynamic stability in patients with a rapidly changing volume status for a short term period, such as during puerperium.
body composition; hemodialysis; postpartum period; volume control
Hyponatremia is a relatively common electrolyte disorder. Although severe acute hyponatremia following coronary angiography is rare, potentially lethal neurologic manifestations may result. We describe a patient with severe, symptomatic hyponatremia, an unusual complication of coronary angiography. Lack of familiarity with contrast media-related hyponatremia caused a delay in diagnosis and therapy in our case. The diagnosis of acute hyponatremia should be considered in any patient who develops behavioral or neurologic manifestations following coronary angiography. Prompt diagnosis and treatment is essential to avoid permanent neurologic damage or death.
Hyponatremia; Coronary angiography
Mineral metabolism abnormalities, such as low 1,25-dihydroxyvitamin D (1,25(OH)2D) and elevated parathyroid hormone (PTH), are common at even higher glomerular filtration rate than previously described. Levels of 25-hydroxyvitamin D (25(OH)D) show an inverse correlation with those of intact PTH and phosphorus. Studies of the general population found much higher all-cause and cardiovascular (CV) mortality for patients with lower levels of vitamin D; this finding suggests that low 25(OH)D level is a risk factor and predictive of CV events in patients without chronic kidney disease (CKD). 25(OH)D/1,25(OH)2D becomes deficient with progression of CKD. Additionally, studies of dialysis patients have found an association of vitamin D deficiency with increased mortality. Restoration of the physiology of vitamin D receptor activation should be essential therapy for CKD patients.
renal insufficiency, chronic; vitamin D; deficiency
Atherosclerotic renovascular hypertension is a form of secondary hypertension due to renal artery stenosis. After the introduction of medical therapy such as with statins and angiotensin blocking agents, it has been considered a very slowly progressive disease. In the 1990s, surgical methods were compared to radiological intervention and showed no additional benefits. Recent clinical data also demonstrate that in cases of relatively stable atherosclerotic renovascular disease, medical therapy is as effective as other interventions with regard to patient outcomes. In this paper the recent clinical outcomes are reviewed.
atherosclerosis; renal artery obstruction; hypertension
Thiazide is known to decrease urinary calcium excretion. We hypothesized that thiazide shows different hypocalciuric effects depending on the stimuli causing hypercalciuria. The hypocalciuric effect of hydrochlorothiazide (HCTZ) and the expression of transient receptor potential vanilloid 5 (TRPV5), calbindin-D28K, and several sodium transporters were assessed in hypercalciuric rats induced by high calcium diet and vitamin D3. Urine calcium excretion and the expression of transporters were measured from 4 groups of Sprague-Dawley rats; control, HCTZ, high calcium-vitamin D, and high calcium-vitamin D with HCTZ groups. HCTZ decreased urinary calcium excretion by 51.4% in the HCTZ group and only 15% in the high calcium-vitamin D with HCTZ group. TRPV5 protein abundance was not changed by HCTZ in the high calcium-vitamin D with HCTZ group compared to the high calcium-vitamin D group. Protein abundance of NHE3, SGLT1, and NKCC2 decreased in the hypercalciuric rats, and only SGLT1 protein abundance was increased by HCTZ in the hypercalciuric rats. The hypocalciuric effect of HCTZ is attenuated in high calcium and vitamin D-induced hypercalciuric rats. This attenuation seems to have resulted from the lack of HCTZ's effect on protein abundance of TRPV5 in severe hypercalciuric condition induced by high calcium and vitamin D.
Hypercalciuria; TRPV5; Sodium Transporters; Cholecalciferol; Thiazides
The long-term clinical benefits of vascular access blood flow (VABF) measurements in hemodialysis (HD) patients have been controversial. We evaluated whether early VABF may predict long-term vascular access (VA) patency in incident HD patients. We enrolled 57 patients, of whom 27 were starting HD with arteriovenous fistulas (AVFs) and 30 with arteriovenous grafts (AVGs). The patients' VABF was measured monthly with the ultrasound dilution technique over the course of the first six months after the VA operation. During the 20.4-month observational period, a total of 40 VA events in 23 patients were documented. The new VA events included 13 cases of stenosis and 10 thrombotic events. The lowest quartile of average early VABF was related to the new VA events. After adjusting for covariates such as gender, age, hypertension, diabetes, VA type, hemoglobin levels, body mass index, parathyroid hormone, and calcium-phosphorus product levels, the hazard ratio of VABF (defined as <853 mL/min in AVF or <830 mL/min in AVG) to incident VA was 3.077 (95% confidence interval, 1.127-8.395; P=0.028). There were no significant relationships between early VABF parameters and VA thrombosis. It is concluded that early VABF may predict long-term VA patency, particularly VA stenosis.
Renal Dialysis; Blood Flow Velocity; Vascular Patency; Indicator Dilution Techniques
Uninephrectomy (uNx) in young rats causes salt-sensitive hypertension (SSH). Alterations of sodium handling in residual nephrons may play a role in the pathogenesis. Therefore, we evaluated the adaptive alterations of renal sodium transporters according to salt intake in uNx-SSH rats. uNx or sham operations were performed in male Sprague-Dawley rats, and normal-salt diet was fed for 4 weeks. Four experimental groups were used: sham-operated rats raised on a high-salt diet for 2 weeks (CHH) or on a low-salt diet for 1 week after 1 week's high-salt diet (CHL) and uNx rats fed on the same diet (NHH, NHL) as the sham-operated rats were fed. Expression of major renal sodium transporters were determined by semiquantitative immunoblotting. Systolic blood pressure was increased in NHH and NHL groups, compared with CHH and CHL, respectively. Protein abundances of Na+/K+/2Cl- cotransporter (NKCC2) and Na+/Cl- cotransporter (NCC) in the CHH group were lower than the CHL group. Expression of epithelial sodium channel (ENaC)-γ increased in the CHH group. In contrast, expressions of NKCC2 and NCC in the NHH group didn't show any significant alterations, compared to the NHL group. Expressions of ENaC-α and ENaC-β in the NHH group were higher than the CHH group. Adaptive alterations of NKCC2 and NCC to changes of salt intake were different in the uNx group, and changes in ENaC-α and ENaC-β were also different. These altered regulations of sodium transporters may be involved in the pathogenesis of SSH in the uNx rat model.
salt-sensitive hypertension; nephrectomy; sodium-potassium-chloride symporters; sodium chloride symporters; epithelial sodium channel
Hypokalemia occurs frequently in patients undergoing peritoneal dialysis (PD). However, the therapeutic strategy may differ from that of non-PD-related hypokalemia. We investigated clinical features and related factors of de novo hypokalemia in incident PD patients. We retrospectively enrolled 82 normokalemic patients starting PD at Gachon University Gil Hospital, Korea. The patients were divided into hypokalemia (K+<3.5 mEq/L) and normokalemia (3.5 mEq/L≤K+<5.5 mEq/L) groups based on the plasma potassium levels at month 13, and then clinical parameters including peritoneal function and adequacy tests and biochemical parameters were compared. Eight patients who showed hyperkalemia (K+≥5.5 mEq/L) at month 13 were excluded from our analyses. The incidence of hypokalemia in PD patients was 7.3% in a year. The de novo hypokalemia (n=6) and normokalemia (n=68) groups had no significant differences in baseline characteristics. The serum albumin levels and normalized protein equivalent of nitrogen appearance (nPNA) at month 1 were not significantly different between the two groups. At month 13, on the other hand, serum albumin levels and nPNA were significantly lower in the hypokalemia group (P=0.014; P=0.006, respectively). Kt/Vurea, residual renal function, dialysate-peritoneal creatinine ratio, and glucose load were not significantly different between the two groups. Hypokalemia occurring after initiation of PD may largely be associated with poor nutritional status.
hypokalemia; peritoneal dialysis; serum albumin; nutrition
Pendrin (SLC26A4) is a Na+-independent Cl-/HCO3- exchanger which is expressed in the apical membranes of type B and non-A, non-B intercalated cells within the distal convoluted tubule, the connecting tubule, and the cortical collecting duct. In those segments it mediates HCO3- secretion and chloride (Cl-) absorption. In mice, no renal abnormalities are observed under basal conditions, and individuals with genetic disruption of the pendrin (SLC26A4) gene (Pendred syndrome) have normal acid-base balance. In contrast, there are definite differences under conditions wherein the transporter is stimulated. In animal studies, pendrin (SLC26A4) is upregulated with aldosterone analogues, Cl- restriction, and metabolic alkalosis, and is down-regulated with Cl loading and metabolic acidosis, independently. However, the exact role of pendrin in humans has not been established to date, and further examinations are necessary.
pendrin; SLC26A4; acidosis, renal tubular; metabolic alkalosis
We determined the relationship between the progression of immunoglobulin A nephropathy (IgAN) and the A1818T polymorphism in intron 2 of Angiotensin II type 2 receptor (AT2R) gene, which might play protective roles in the pathogenesis of IgAN. Patients with biopsy-proven IgAN were recruited from the registry of the Progressive REnal disease and Medical Informatics and gEnomics Research (PREMIER) which was sponsored by the Korean Society of Nephrology. A1818T polymorphism of AT2R gene was analyzed with PCR-RFLP method and the association with the progression of IgAN, which was defined as over 50% increase in baseline serum creatinine level, was analyzed with survival analysis. Among the 480 patients followed for more than 10 months, the group without T allele had significantly higher rates of progression of IgAN than the group with T allele (11.4% vs. 3.9%, p=0.024), although there were no significant differences in the baseline variables such as initial serum creatinine level, the degree of proteinuria, and blood pressure. In the Cox's proportional hazard model, the hazard ratio of disease progression in the patients with T allele was 0.221 (95% confidence interval for Exp(B): 0.052-0.940, p=0.041) compared to that of without T allele. In conclusion, A1818T polymorphism of AT2R gene was associated with the progression of IgAN.
Polymorphism, Single Nucleotide; Glomerulonephritis, IGA; Receptor, Angiotensin, Type 2
TRPV5 is believed to play an important role in the regulation of urinary calcium excretion. We assessed the effects of hydrochlorothiazide (HCTZ) on the expression of TRPV5, calbindin-D28K, and several sodium transporters in hypercalciuric rats. Sprague-Dawley rats were divided into 4 groups; control, HCTZ, high salt, and high salt with HCTZ group in experiment 1; control, HCTZ, high calcium (Ca), and high Ca with HCTZ group in experiment 2. To quantitate the expression of TRPV5, calbindin-D28K, and sodium transporters, western blotting was performed. In both experiments, HCTZ significantly decreased urinary calcium excretion. TRPV5 protein abundance decreased in all hypercalciuric rats, and restored by HCTZ in both high salt with HCTZ and high Ca with HCTZ group. Calbindin-D28K protein abundance increased in the high salt and high salt with HCTZ groups, but did not differ among groups in experiment 2. Protein abundance of NHE3 and NKCC2 decreased in all hypercalciuric rats, and were restored by HCTZ in only high Ca-induced hypercalciuric rats. In summary, protein abundance of TRPV5, NHE3, and NKCC2 decreased in all hypercalciuric rats. The hypocalciuric effect of HCTZ is associated with increased protein abundance of TRPV5 in high salt or calcium diet-induced hypercalciuric rats.
Hypercalciuria; Thiazides; Transporters