Chronic kidney disease (CKD) has been recognized as a significant global health problem because of the increased risk of total and cardiovascular morbidity and mortality. Vitamin D deficiency or insufficiency is common in patients with CKD, and serum levels of vitamin D appear to have an inverse correlation with kidney function. Growing evidence has indicated that vitamin D deficiency may contribute to deteriorating renal function, as well as increased morbidity and mortality in patients with CKD. Recent studies have suggested that treatment with active vitamin D or its analogues can ameliorate renal injury by reducing fibrosis, apoptosis, and inflammation in animal models; this treatment also decreases proteinuria and mortality in patients with CKD. These renoprotective effects of vitamin D treatment are far beyond its classical role in the maintenance of bone and mineral metabolism, in addition to its pleiotropic effects on extra-mineral metabolism. In this review, we discuss the altered metabolism of vitamin D in kidney disease, and the potential renoprotective mechanisms of vitamin D in experimental and clinical studies. In addition, issues regarding the effects of vitamin D treatment on clinical outcomes are discussed.
Vitamin D; Renal insufficiency, chronic; Cardiovascular diseases; Mortality
The present study aimed to investigate the impact of high-sensitivity C-reactive protein (hs-CRP) and renal dysfunction on clinical outcomes in acute myocardial infarction (AMI) patients.
Materials and Methods
The study involved a retrospective cohort of 8332 patients admitted with AMI. The participants were divided into 4 groups according to the levels of estimated glomerular filtration rate (eGFR) and hs-CRP: group I, no renal dysfunction (eGFR ≥60 mL·min-1·1.73 m-2) with low hs-CRP (≤2.0 mg/dL); group II, no renal dysfunction with high hs-CRP; group III, renal dysfunction with low hs-CRP; and group IV, renal dysfunction with high hs-CRP. We compared major adverse cardiac events (MACE) over a 1-year follow-up period.
The 4 groups demonstrated a graded association with increased MACE rates (group I, 8.8%; group II, 13.8%; group III, 18.6%; group IV, 30.1%; p<0.001). In a Cox proportional hazards model, mortality at 12 months increased in groups II, III, and IV compared with group I [hazard ratio (HR) 2.038, 95% confidence interval (CI) 1.450-2.863, p<0.001; HR 3.003, 95% CI 2.269-3.974, p<0.001; HR 5.087, 95% CI 3.755-6.891, p<0.001].
High hs-CRP, especially in association with renal dysfunction, is related to the occurrence of composite MACE, and indicates poor prognosis in AMI patients.
C-reactive protein; glomerular filtration rate; myocardial infarction
The present study aimed to investigate changes in the mammalian target of rapamycin (mTOR) signaling pathway in the obstructed kidney of rats with unilateral ureteral obstruction (UUO). Male Sprague-Dawley rats were unilaterally obstructed by ligation of the left proximal ureter for 7 days. Control rats were treated in the same way except that no ligature was made. The expression levels of phosphorylated phosphatidylinositol 3-kinase (PI3K), Akt, and mTOR were determined in the kidney by semiquantitative immunoblotting. The protein expression levels of transforming growth factor (TGF)-β1, Bax, and Bcl-2 were also determined in the kidney. The phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of ureteral obstruction rats compared with the control. In the obstructed kidney, the protein expression of TGF-β1 and Bax was also increased, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the obstructed kidney of rats with UUO.
mTOR protein, rat; Ureteral Obstruction; Fibrosis; Apoptosis
While the anti-apoptotic effect of paricalcitol has been demonstrated in various animal models, it is not yet clear whether paricalcitol attenuates the apoptosis in gentamicin (GM)-induced kidney injury. We investigated the effect of paricalcitol on apoptotic pathways in rat kidneys damaged by GM. Rats were randomly divided into three groups: 1) Control group (n=8), where only vehicle was delivered, 2) GM group (n=10), where rats were treated with GM (150 mg/kg/day) for 7 days, 3) PARI group (n=10), where rats were co-treated with paricalcitol (0.2 µg/kg/day) and GM for 7 days. Paricalcitol attenuated renal dysfunction by GM administration in biochemical profiles. In terminal deoxynucleotidyl transferase dUTP nick end labeling staining, increased apoptosis was observed in GM group, which was reversed by paricalcitol co-treatment. Immunoblotting using protein samples from rat cortex/outer stripe of outer medulla showed increased Bax/Bcl-2 ratio and cleaved form of caspase-3 in GM group, both of which were reversed by paricalcitol. The phosphorylated Jun-N-terminal kinase (JNK) expression was increase in GM, which was counteracted by paricalcitol. The protein expression of p-Akt and nitro-tyrosine was also enhanced in GM-treated rats compared with control rats, which was reversed by paricalcitol co-treatment. Paricalcitol protects GM-induced renal injury by antiapoptotic mechanisms, including inhibition of intrinsic apoptosis pathway and JNK.
Apoptosis; Gentamicin; Kidney; Paricalcitol
We investigated the effects of proteinuria and renal insufficiency on all-cause mortality in patients with colorectal cancer, with special emphasis on cancer staging and cancer-related deaths.
Materials and Methods
We retrospectively studied a cohort of patients with colorectal cancer. In protocol 1, patients were classified into four groups based on the operability of cancer and proteinuria: group 1, early-stage cancer patients (colorectal cancer stage ≤3) without proteinuria; group 2, early-stage cancer patients with proteinuria; group 3, advanced-stage cancer patients without proteinuria (colorectal cancer stage=4); and group 4, advanced-stage cancer patients with proteinuria. In protocol 2, patients were classified into four similar groups based on cancer staging and renal insufficiency (eGFR <60 mL/min/1.73 m2). Between January 1, 1998 and December 31, 2009, 3379 patients were enrolled in this cohort and followed until May 1, 2012 or until death.
The number of patients with proteinuria was 495 (14.6%). The prevalence of proteinuria was higher in advanced-stage cancer (n=151, 22.3%) than in early-stage cancer patients (n=344, 12.7%). After adjusting for age, gender and other clinical variables, the proteinuric, early-stage cancer group was shown to be associated with an adjusted hazard ratio of 1.67 and a 95% confidence interval of 1.38-2.01, compared with non-proteinuric early-stage cancer patients. However, renal insufficiency was not associated with colorectal cancer mortality.
Proteinuria is an important risk factor for cancer mortality, especially in relatively early colorectal cancer.
Cancer; death; proteinuria; GFR; stage
The aim of this study was to investigate clinical characteristics and risk factors of acute kidney injury (AKI) in patients with sepsis and septic shock. Additionally, we explored whether the severity of AKI affects on the clinical outcomes.
Materials and Methods
Data were collected retrospectively in a single center. Among 5680 patients who visited emergency department from January to December 2010, 992 patients with sepsis and septic shock were enrolled. Patients were divided into two groups, patients who developed AKI or not, to compare the baseline characteristics, and laboratory and physiologic data. Patients with AKI were subdivided according to its stages for survival analysis.
AKI was developed in 57.7% of patients. Multivariable logistic regression analysis revealed that development of septic AKI was associated with older age, pre-existing chronic kidney disease, use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker, presence of shock, positive blood culture results, and low white blood cell and platelet counts. Hospital mortality was higher in AKI group. Crude Kaplan-Meier survival curves demonstrated reduced 30-day survival rate was significantly associated with the severity of acute kidney injury.
The development of septic AKI was associated with poor clinical outcomes. Furthermore, the severity of AKI was associated with increased mortality.
Acute kidney injury; mortality; risk factors; sepsis; septic shock
This study aimed to evaluate the effects of percutaneous coronary intervention (PCI) on short- and long-term major adverse cardiac events (MACE) in elderly (>75 yr old) acute myocardial infarction (AMI) patients with renal dysfunction. As part of Korea AMI Registry (KAMIR), elderly patients with AMI and renal dysfunction (GFR<60 mL/min) received either medical (n=439) or PCI (n=1,019) therapy. Primary end point was in-hospital death. Secondary end point was MACE during a 1 month and 1 yr follow-up. PCI group showed a significantly lower incidence of in-hospital death (20.0% vs 14.3%, P=0.006). Short-term and long-term MACE rates were higher in medical therapy group (31.9% vs 19.0%; 57.7% vs 31.3%, P<0.001), and this difference was mainly attributed to cardiac death (29.3% vs 17.6%; 51.9% vs 25.0%, P<0.001). MACE-free survival time after adjustment was also higher in PCI group on short-term (hazard ratio, 0.67; confidence interval, 0.45-0.98; P=0.037) and long-term follow-up (hazard ratio, 0.61, confidence interval, 0.45-0.83; P=0.002). In elderly AMI patients with renal dysfunction, PCI therapy yields favorable in-hospital and short-term and long-term MACE-free survival.
Acute Myocardial Infarction; Renal Dysfunction; Elderly; Percutaneous Coronary Intervention; Major Adverse Cardiac Event
A 27-year-old man presented to the emergency department with sudden onset of massive gross hematuria and urinary retention. Contrast-enhanced computed tomography imaging showed uneven, dilated calices and a narrowing of the renal pelvis in the left kidney; in addition, a large hematoma was noted in the urinary bladder. An emergency cystoscopy was performed following detection of the hematoma and blood clots were removed. A lesional biopsy, a tuberculosis (TB) culture, and urine cytology showed positive results for Mycobacterium tuberculosis. The clinical manifestations of genitourinary tuberculosis are nonspecific and are usually detected at a chronic stage. In conclusion, we report an unusual cause of acute kidney injury associated with a subacute stage of genitourinary tuberculosis that caused mucosal erosion and bleeding in the bladder.
Tuberculosis; Acute kidney injury; Hematuria
We report a case of Serratia marcescens peritonitis in a 45-year-old man with insulin-dependent diabetes mellitus undergoing continuous ambulatory peritoneal dialysis (CAPD). The patient presented with abdominal pain and cloudy dialysate. Empiric antibiotic therapy was initiated intraperitoneally with cefazolin and ceftazidime for 5 days. Cultures of the dialysate revealed S. marcescens, and the treatment was subsequently changed to gentamicin and ceftazidime. Oral ciprofloxacin was also added. The patient's abdominal pain and the dialysate white blood cell (WBC) count, however, did not improve. The indwelling CAPD catheter was therefore removed. This is an unusual case report in the Korean literature of S. marcescens peritonitis in a patient receiving CAPD.
Serratia marcescens; Continuous ambulatory peritoneal dialysis; Peritonitis
The present study investigated the changes that occurred in the mammalian target of rapamycin (mTOR) signaling pathway in the kidney as a result of deoxycorticosterone acetate (DOCA)-salt hypertension. Rats were implanted with DOCA strips (200 mg/kg) 1 week after unilateral nephrectomy and were then supplied with 0.9% saline to drink. Four weeks after DOCA implantation, systolic blood pressure (SBP) was measured by use of the tail-cuff method. The expression levels of phosphorylated phosphatidylinositol-3-kinase (PI3K), Akt, and mTOR, as well as the protein expression levels of ED-1 and cyclooxygenase-2 (COX-2), transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (SMA), caspase-3, Bax, and Bcl-2, were then examined in the kidney by semiquantitative immunoblotting. DOCA-salt hypertensive rats were found to have significantly increased SBP as well as an increased kidney weight-to-body weight ratio. Moreover, the phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of DOCA-salt hypertensive rats compared with the control, as was the protein expression of ED-1, COX-2, TGF-β1, and α-SMA. The expression levels of caspase-3 and Bax were increased significantly, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the kidney of DOCA-salt hypertensive rats.
Deoxycorticosterone; Hypertension; Kidney
A 59-year-old female with diabetes mellitus presented with hypercalcemia and polycythemia. Her serum calcium and intact parathyroid hormone (iPTH) levels were increased, and Tc-99m sesta-MIBI scanning showed hot uptake in the lower portion of the left thyroid lobe. After parathyroidectomy, her calcium, iPTH, and polycythemia were normalized. In conclusion, the differential diagnosis of polycythemia and hypercalcemia should also include the possibility of a parathyroid tumor in addition to other neoplasms.
Hypercalcemia; Polycythemia vera; Parathyroid tumor
The role of the kidney in combating metabolic acidosis has been a subject of considerable interest for many years. The present study was aimed to determine whether there is an altered regulation of renal acid base transporters in acute and chronic acid loading. Male Sprague-Dawley rats were used. Metabolic acidosis was induced by administration of NH4Cl for 2 days (acute) and for 7days (chronic). The serum and urinary pH and bicarbonate were measured. The protein expression of renal acid base transporters [type 3 Na+/H+ exchanger (NHE3), type 1 Na+/HCO3- cotransporter (NBC1), Na-K+ ATPase, H+-ATPase, anion exchanger-1 (AE-1)] was measured by semiquantitative immunoblotting. Serum bicarbonate and pH were decreased in acute acid loading rats compared with controls. Accordingly, urinary pH decreased. The protein expression of NHE3, H+-ATPase, AE-1 and NBC1 was not changed. In chronic acid loading rats, serum bicarbonate and pH were not changed, while urinary pH was decreased compared with controls. The protein expression of NHE3, H+-ATPase was increased in the renal cortex of chronic acid loading rats. These results suggest that unaltered expression of acid transporters combined with acute acid loading may contribute to the development of acidosis. The subsequent increased expression of NHE3, H+-ATPase in the kidney may play a role in promoting acid excretion in the later stage of acid loading, which counteract the development of metabolic acidosis.
Ammonium chloride; Acidosis; Sodium-hydrogen exchanger 3; Proton-Translocating ATPases
A 30-year-old male presented with pitting edema. He had received a kidney transplantation 3 months previously. His serum creatinine level was increased, and a renal ultrasound showed hypoechoic fluid collection in the perirenal space and pelvic cavity. We conducted sono-guided percutaneous drainage of the fluid collected in the pelvic cavity. The chemistry of the peritoneal fluid was more equivalent to serum chemistry values than to urinary values. Simple aspiration and treatment with antibiotics were performed. We have presented a case of lymphocele after kidney transplantation. This case suggests that physicians should remember how to differentiate the pelvic cavity fluid collection in patients who have received a kidney transplant.
Lymphocele; Kidney; Transplantation
We report the case of a female patient with incomplete distal renal tubular acidosis with nephrocalcinosis. She was admitted to the hospital because of acute pyelonephritis. Imaging studies showed dual medullary nephrocalcinosis. Subsequent evaluations revealed hypokalemia, hypocalcemia, hypercalciuria, and hypocitraturia with normal acid-base status. A modified tubular acidification test with NH4Cl confirmed a defect of urine acidification, which is compatible with incomplete distal tubular acidosis. We treated our patient with potassium citrate, which corrects hypokalemia and prevents further deposition of calcium salts.
Renal tubular acidosis; Nephrocalcinosis; Kidney
Nitric oxide (NO) and atrial natriuretic peptide (ANP) may induce vascular relaxation by increasing the production of cyclic guanosine monophosphate (cGMP), an important mediator of vascular tone during sepsis. This study aimed to determine whether regulation of NO and the ANP system is altered in lipopolysaccharide (LPS)-induced kidney injury. LPS (10 mg.kg-1) was injected in the tail veins of male Sprague-Dawley rats; 12 hours later, the kidneys were removed. Protein expression of NO synthase (NOS) and neutral endopeptidase (NEP) was determined by semiquantitative immunoblotting. As an index of synthesis of NO, its stable metabolites (nitrite/nitrate, NOx) were measured using colorimetric assays. mRNA expression of the ANP system was determined by real-time polymerase chain reaction. To determine the activity of guanylyl cyclase (GC), the amount of cGMP generated in response to sodium nitroprusside (SNP) and ANP was calculated. Creatinine clearance decreased and fractional excretion of sodium increased in LPS-treated rats compared with the controls. Inducible NOS protein expression increased in LPS-treated rats, while that of endothelial NOS, neuronal NOS, and NEP remained unchanged. Additionally, urinary and plasma NOx levels increased in LPS-treated rats. SNP-stimulated GC activity remained unchanged in the glomerulus and papilla in the LPS-treated rats. mRNA expression of natriuretic peptide receptor (NPR)-C decreased in LPS-treated rats, while that of ANP and NPR-A did not change. ANP-stimulated GC activity reduced in the glomerulus and papilla. In conclusion, enhancement of the NO/cGMP pathway and decrease in ANP clearance were found play a role in the pathogenesis of LPS-induced kidney injury.
Lipopolysaccharide; Atrial natriuretic peptide; Nitric oxide; Guanylyl cyclase
A 59-year-old man with confused mental status was admitted to our hospital. Laboratory reports showed him to have severe hyponatremia, and additional studies revealed panhypopituitarism. Brain magnetic resonance imaging showed a sellar cystic lesion, which consisted of a Rathke cleft cyst. Thus, the mass effect of the Rathke cleft cyst resulted in panhypopituitarism and finally induced euvolemic hyponatremia. On the basis of these results, supplementation with thyroid hormone and glucocorticoid was started, and the patient's serum sodium level was gradually corrected and maintained within the normal range. Here, we report this case of euvolemic hyponatremia caused by a Rathke cleft cyst.
Rathke cleft cyst; Hyponatremia; Panhypopituitarism
This study aimed to compare the incidence and clinical significance of transient versus persistent acute kidney injury (AKI) on acute ST elevation myocardial infarction (STEMI).
Materials and Methods
The study was a retrospective cohort of 855 patients with STEMI. AKI was defined as an increase of ≥0.3 mg/dL in creatinine level at any point during hospital stay. The study population was classified into 5 groups: 1) patients without AKI; 2) patients with mild AKI that was resolved by discharge (creatinine change less than 0.5mg/dL compared with admission creatinine during hospital stay, transient mild AKI); 3) patients with mild AKI that did not resolve by discharge (persistent mild AKI); 4) patients with moderate/severe AKI that was resolved by discharge (creatinine change more than 0.5 mg/dL compared with admission creatinine, transient moderate/severe AKI); 5) patients with moderate/severe AKI that did not resolve by discharge (persistent moderate/severe AKI). We investigated 1-year all-cause mortality after hospital discharge for the primary outcome of the study. The relation between AKI and 1-year mortality after STEMI was analyzed.
AKI occurred in 74 (8.7%) patients during hospital stay. Adjusted hazard ratio for mortality was 3.139 (95% CI 0.764 to 12.897, p=0.113) in patients with transient, mild AKI, and 8.885 (95% CI 2.710 to 29.128, p<0.001) in patients with transient, moderate/severe AKI compared to patients without AKI. Persistent moderate/severe AKI was also independent predictor of 1 year mortality (hazard ratio, 5.885; 95% CI 1.079 to 32.101, p=0.041).
Transient and persistent moderate/severe AKI during acute myocardial infarction is strongly related to 1-year all cause mortality after STEMI.
Acute kidney injury; myocardial infarction; mortality
A 34-year-old female presented with end-stage renal disease (ESRD) treated by peritoneal dialysis (CAPD) complained of a dry cough. Chest X-ray and chest computed tomography (CT) scan revealed massive right hydrothorax. Because the glucose concentration of pleural fluid was markedly high compared with that of serum, we performed isotope and contrast peritoneography. We used CT for localizing it. MRI was also trying to show transdiaphragmatic leakage in peritoneoflural fistula. Temporary discontinuation of CAPD, tetracycline instillation into the pleural space and surgical patch grafting of the diaphragmatic leak have all been described. A novel method may be video-assisted talc pleurodesis.
Pleural effusion; Dialysis; Kidney
The collecting duct endothelin (ET) system, which involves ET-1 and its two receptors, may play a role in the regulation of renal sodium in association with the nitric oxide synthase (NOS) system. We determined whether sodium retention is associated with changes in the endothelin and NOS systems at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndromes. On day 7 after puromycin aminonucleoside (PAN) injection, urinary sodium excretion was decreased, ascites had developed, and there was a positive sodium balance. ET-1 mRNA expression was increased in the inner medulla of the kidney, whereas protein expression of ET receptor type B (ETBR) was unchanged. The expression of neuronal NOS (nNOS) was decreased in the inner medulla. On day 14, urinary sodium excretion was unchanged compared with controls. The expression of ETBR increased, while nNOS expression in the inner medulla was comparable to controls. These findings suggest that decreased nNOS plays a role in the development of sodium retention in the nephrotic syndrome. Recovery of nNOS and increased renal ETBR synthesis may promote sodium excretion in later stages of the nephrotic syndrome (on day 14).
Nephrotic syndrome; Endothelin receptor type B; Nitric oxide synthase; Puromycin aminonucleoside
The present study aimed to compare the clinical outcomes and to investigate prognostic factors of acute coronary syndrome (ACS) in patients with renal dysfunction (RD).
Materials and Methods
The study was a retrospective cohort of 648 adult patients admitted with ACS between October 2005 and December 2006. The estimated glomerular filtration rate (GFR) was classified into 4 levels: 1) normal, GFR greater than 90 mL/min/1.73 m2; 2) mild RD, GFR of 60 to 90 mL/min/1.73 m2; 3) moderate RD, GFR of 30 to 60 mL/min/1.73 m2; and 4) severe RD, GFR less than 30 mL/min/1.73 m2. Primary end points were death and complication in hospital courses. Secondary end points were major adverse cardiac event (MACE) during follow-up.
The median follow-up was 505 ± 183 days, the mean age was 63 ± 12 years, and 71.8 percent of the group were men. A graded association was observed between severity of RD and clinical outcomes. Severe RD independently predicted MACE [hazard ratio, 2.731; 95% confidence interval (CI), 1.058 to 7.047, p = 0.038]. Low hemoglobin level was also an independent risk factor for MACE (hazard ratio, 1.155; 95% CI, 1.020 to 1.307, p = 0.022). Use of lipid-lowering therapy (hazard ratio, 0.456; 95% CI, 0.242 to 0.857, p = 0.015) was associated with reduced risk for MACE.
Severe RD and low hemoglobin level were an independent risk factors for the mortality and complications of ACS, while lipid-lowering therapy was associated with reduced risk.
Acute coronary syndrome; glomerular filtration rate; risk factors
Sodium retention is a hallmark of nephrotic syndrome. We investigated whether sodium retention is associated with changes of natriuretic peptide system at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndrome. At day 7 after PAN (puromycin aminonucleoside) injection, the urinary excretion of sodium was decreased, along with the development of ascites and positive sodium balance. The plasma and urinary ANP (atrial natriuretic peptide) immunoreactivities were increased. ANP mRNA expression was increased in the heart and kidney, whereas that of NPR (natriuretic peptide receptor)-A and NPR-C mRNA was decreased in the kidney. The expression of NEP was decreased in the kidney. At day 14, urinary excretion of sodium did not differ from the control. The plasma ANP level and heart ANP mRNA expression returned to their control values. The expression of ANP mRNA in the kidney was increased in association with increased urinary ANP immunoreactivities. The expression of NPR-A in the kidney became normal, whereas that of NPR-C kept decreased. The expression of NEP (neutral endopeptidase) remained decreased. These findings suggest that the increased renal ANP synthesis in association with decreased metabolism via NEP and NPR-C may play a compensatory role against the development of sodium retention in nephrotic syndrome. The decreased of NPR-A expression in the kidney may contribute to the ANP resistance at day 7. The subsequent recovery of NPR-A expression may play a role in promoting sodium excretion in later stage (at day 14).
Nephrotic syndrome; Natriuretic peptide; Puromycin aminonucleoside
The present study was aimed to determine whether there is an altered regulation of tubular transporters in gentamicin-induced nephropathy. Sprague-Dawley male rats (200~250 g) were subcutaneously injected with gentamicin (100 mg/kg per day) for 7 days, and the expression of tubular transporters was determined by immunoblotting and immunohistochemistry. The mRNA and protein expression of OAT was also determined. Gentamicin-treated rats exhibited significantly decreased creatinine clearance along with increased plasma creatinine levels. Accordingly, the fractional excretion of sodium increased. Urine volume was increased, while urine osmolality and free water reabsorption were decreased. Immunoblotting and immunohistochemistry revealed decreased expression of Na+/K+-ATPase, NHE3, NBC1, and AQP1 in the kidney of gentamicin-treated rats. The expression of OAT1 and OAT3 was also decreased. Gentamicin-induced nephropathy may at least in part be causally related with a decreased expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT.
Gentamicin; Sodium transporters; Aquaporin-1; Organic anion transporters
The deoxycorticosterone acetate (DOCA)-salt rat is known as a model of volume dependent hypertension and characterized by increased cardiac endothelin-1 (ET-1) content. Recently, it has been reported that rosiglitazone (RGT), a peroxisome proliferator-activated subtype gamma receptor agonist, shows blood pressure lowering effect. We investigated whether DOCA-salt hypertension is associated with altered expression of heat shock proteins (HSP) and ET-1 in the heart, aorta, and kidney, and whether RGT changes HSP expression and ET-1 in association with its blood pressure lowering effect. Two weeks after the silastic DOCA (200 mg/kg) strips implantation, DOCA-salt rats were randomly divided to receive control diet with or without RGT (10 mg/kg/day) for another 2 weeks. The mRNA expression of ET-1 was determined by real time polymerase chain reaction. The expression of HSP was determined by semiquantitative immunoblotting. In DOCA-salt rats, systolic blood pressure was markedly increased, while creatinine clearance decreased. RGT treatment attenuated high blood pressure and decreased creatinine clearance in DOCA-salt rats. The mRNA expression of ET-1 was increased in DOCA-salt rats compared to controls, which was counteracted by RGT treatment. The protein expression of HSP70, HSP32, and HSP25 was increased in the kidney and heart in DOCA-salt rats, which was attenuated by RGT treatment in the kidney, but not in the heart. In conclusion, increased expression of ET-1 may play a role in the pathogenesis of hypertension in DOCA-salt rats, which was counteracted by the treatment of RGT. Up-regulation of HSP70, HSP32, and HSP25 in the kidney and heart may play a role in organ protection against a variety of stresses.
rosiglitazone; heat-shock proteins; deoxycorticosterone acetate-salt; endothelin-1
Metabolic acidosis was shown to correlate with deterioration of renal function in patients with rhabdomyolysis. The present study was aimed to investigate whether the changes of type 3 Na+/H+ exchanger (NHE3), type 1 Na+/HCO3- cotransporter (NBC1), and Na+,K+-ATPase α1 subunit may play a role in the pathogenesis of metabolic acidosis in glycerol-induced experimental rhabdomyolysis. Male Sprague-Dawley rats were deprived of fluid intake for 24 hours, and then were injected with 50% glycerol in normal saline (10 mL/kg, intramuscularly). At 24 hours after the glycerol injection, rats were sacrificed by decapitation. Control rats were injected with normal saline. The protein expression of NHE3, NBC1 and Na+,K+-ATPase α1 subunit was determined in the cortex of the kidney by immunoblotting and immunohistochemistry. Following the treatment of glycerol, creatinine clearance was significantly decreased, and high anion gap metabolic acidosis developed. In the experimental group, the expression of Na+,K+-ATPase α1 subunit was significantly decreased in the cortex of the kidney. On the contrary, the expression of NHE3 and NBC1 was significantly increased. Immunohistochemical analyses confirmed the immunoblotting data. In conclusion, the coordinate up-regulation of NHE3 and NBC1 may play an adaptive role against the metabolic acidosis in glycerol-induced rhabdomyolysis.
Rhabdomyolysis; Metabolic acidosis; Type 3 Na+/H+ exchanger; Type 1 Na+/HCO3- cotransporter