Update of aristolochic acid nephropathy in Korea

BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSIONS: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.

Effects of colchicine on renal fibrosis and apoptosis in obstructed kidneys

BACKGROUND/AIMS: Colchicine is an established drug for microtubule stabilization that may reduce tissue injury. No data were available that its effects may depend on the dosage of colchicine. We investigated the anti-fibrotic and apoptotic effects of various dose of colchicine in a unilateral ureteral obstruction (UUO) model. METHODS: Thirty-six Sprague-Dawley rats were randomly assigned into six groups. Two sham groups were divided into a vehicle-treated or colchicine-treated group (100 μg/kg/day). Four UUO groups were treated with either vehicle or three different doses of colchicine for 7 days (30, 60, and 100 μg/kg/day, intraperitoneally). All of the animals were sacrificed on day 7. RESULTS: Colchicine treatment diminished acetylated α-tubulin and tumor growth factor-β immunoreactivities in the cortical area of the 7-day obstructed kidneys, which was in dose dependent manner. Colchicine attenuated tubulointerstitial damage and apoptosis in both cortical and medullary area, and beneficial effects of colchicine therapy were dramatically shown at the higher dosage of colchicine. The expression levels of cleaved caspase-3, ED-1, and fibronectin were decreased in UUO animals. CONCLUSIONS: We found that the proper dosage of colchicine may have anti-fibrotic and anti-apoptotic effects in obstructed kidneys. For clinical applications, an optimal dose of colchicine should be evaluated to maximize the prevention of renal disease progression.

Hydrochlorothiazide does not increase furosemide's effects in end-stage renal disease

Diuretic therapy for the treatment of edema in patients with end-stage renal disease (ESRD) is unsatisfactory, and a combination of thiazide and loop diuretics may produce better clinical effects. To evaluate the influence of thiazide on loop diuretic therapy for ESRD, we performed a crossover study of furosemide versus hydrochlorothiazide plus furosemide treatment. The diuretic effects of furosemide (160 mg i.v.) alone versus a combination of hydrochlorothiazide (100 mg p.o.) and furosemide were studied in ten ESRD patients with proteinuria greater than 1 g/day. The diuretic effects were compared for 24 h urine volume and electrolyte excretion. To detect the influence of thiazide that may have been obscured in the widely dispersed data, pharmacodynamic analysis of urine furosemide excretion rate versus fractional excretion of sodium (FeNa) was also performed using mixed-effect modeling. Combination therapy was not significantly different from furosemide monotherapy in terms of 24 h urine volume, chloride, or sodium excretion. Hydrochlorothiazide was not a significant covariate in the furosemide effect for the pharmacodynamic model. In patients with ESRD and severe proteinuria (>1,000 mg/day), the combination of hydrochlorothiazide with furosemide therapy did not increase the diuretic effect of furosemide.

Two Cases of Distal Renal Tubular Acidosis accompanied by Sjogren's Syndrome / 대한내과학회지

Renal tubular acidosis (RTA) is a syndrome characterized by hyperchloremic metabolic acidosis and an inability to excrete highly acid urine, in which the impaired acid excretion is disproportional to the reduction in the glomerular filtration rate. Distal renal tubular acidosis (dRTA) is frequently associated with immune-mediated disease, including Sjogren's syndrome. Sjogren's syndrome is a systemic autoimmune disease that mainly affects exocrine glands, such as the lacrimal and salivary glands, resulting in xerophthalmia and xerostomia. Extraglandular manifestations are frequent and may include renal involvement. Recently, we experienced two cases of renal tubular acidosis in patients with Sjogren's syndrome. The first patient had lower extremity weakness and hypokalemia and the second had nephrocalcinosis. We discuss the frequency and pathogenesis of dRTA in Sjogren's syndrome.

Erratum: Mutations in SLC12A3 and CLCNKB and Their Correlation with Clinical Phenotype in Patients with Gitelman and Gitelman-like Syndrome

I am very sorry to inform you that we made a mistake in description in the original article.

Mutations in SLC12A3 and CLCNKB and Their Correlation with Clinical Phenotype in Patients with Gitelman and Gitelman-like Syndrome

Gitelman's syndrome (GS) is caused by loss-of-function mutations in SLC12A3 and characterized by hypokalemic metabolic alkalosis, hypocalciuria, and hypomagnesemia. Long-term prognosis and the role of gene diagnosis in GS are still unclear. To investigate genotype-phenotype correlation in GS and Gitelman-like syndrome, we enrolled 34 patients who showed hypokalemic metabolic alkalosis without secondary causes. Mutation analysis of SLC12A3 and CLCNKB was performed. Thirty-one patients had mutations in SLC12A3, 5 patients in CLCNKB, and 2 patients in both genes. There was no significant difference between male and female in clinical manifestations at the time of presentation, except for early onset of symptoms in males and more profound hypokalemia in females. We identified 10 novel mutations in SLC12A3 and 4 in CLCNKB. Compared with those with CLCNKB mutations, patients with SLC12A3 mutations were characterized by more consistent hypocalciuria and hypomagnesemia. Patients with 2 mutant SLC12A3 alleles, compared with those with 1 mutant allele, did not have more severe clinical and laboratory findings except for lower plasma magnesium concentrations. Male and female patients did not differ in their requirement for electrolyte replacements. Two patients with concomitant SLC12A3 and CLCNKB mutations had early-onset severe symptoms and showed different response to treatment. Hypocalciuria and hypomagnesemia are useful markers in differentiation of GS and classical Bartter's syndrome. Gender, genotypes or the number of SLC12A3 mutant alleles cannot predict the severity of disease or response to treatment.

Renal adverse effects of sunitinib and its clinical significance: a single-center experience in Korea

BACKGROUND/AIMS: Sunitinib is an oral multitargeted tyrosine kinase inhibitor used mainly for the treatment of metastatic renal cell carcinoma. The renal adverse effects (RAEs) of sunitinib have not been investigated. The aim of this study was to determine the incidence and risk factors of RAEs (proteinuria [PU] and renal insufficiency [RI]) and to investigate the relationship between PU and antitumor efficacy. METHODS: We performed a retrospective review of medical records of patients who had received sunitinib for more than 3 months. RESULTS: One hundred and fifty-five patients (mean age, 58.7 +/- 12.6 years) were enrolled, and the mean baseline creatinine level was 1.24 mg/dL. PU developed in 15 of 111 patients, and preexisting PU was aggravated in six of 111 patients. Only one patient developed typical nephrotic syndrome. Following discontinuation of sunitinib, PU was improved in 12 of 17 patients but persisted in five of 17 patients. RI occurred in 12 of 155 patients, and the maximum creatinine level was 3.31 mg/dL. RI improved in two of 12 patients but persisted in 10 of 12 patients. Risk factors for PU were hypertension, dyslipidemia, and chronic kidney disease. Older age was a risk factor for RI. The median progression-free survival was significantly better for patients who showed PU. CONCLUSIONS: The incidence of RAEs associated with sunitinib was lower than those of previous reports. The severity of RAEs was mild to moderate, and partially reversible after cessation of sunitinib. We suggest that blood pressure, urinalysis, and renal function in patients receiving sunitinib should be monitored closely.

Effects of Sodium Citrate on Salt Sensitivity and Kidney Injury in Chronic Renal Failure

Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.

Alkali Therapy Attenuates the Progression of Kidney Injury via Na/H Exchanger Inhibition in 5/6 Nephrectomized Rats

Metabolic acidosis is a cause of renal disease progression, and alkali therapy ameliorates its progression. However, there are few reports on the role of renal acid-base transporters during alkali therapy. We evaluated the effect of sodium bicarbonate therapy and the role of acid-base transporters on renal disease progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary sodium bicarbonate (NaHCO3) or sodium chloride (NaCl) with 20% casein after a 5/6 nephrectomy. After being provided with a casein diet, the NaHCO3-treated group had higher levels of serum bicarbonate than the control group. At week 4, the glomerular filtration rate in the NaHCO3 group was higher than that in the NaCl group, and the difference became prominent at week 10. The glomerulosclerosis and tubulointerstitial damage indices in the NaHCO3 group were less severe compared with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was decreased, and apical reactivity was decreased in the NaHCO3 group, compared with the NaCl group. Endothelin-1 levels in the kidney were also decreased in the NaHCO3 group. Dietary sodium bicarbonate has the effects of ameliorating renal disease progression, which may be related to the altered expression of NHE in the remaining kidney.

Renal replacement therapy in Korea, 2012

The Korean Society of Nephrology (KSN) launched the official end-stage renal disease (ESRD) patient registry in 1985, and an Internet online registry program was opened in 2001 and revised in 2013. The ESRD Registry Committee of KSN has collected data on dialysis therapy in Korea through the online registry program in the KSN Internet website. The status of renal replacement therapy in Korea at the end of 2012 is described in the following. The total number of ESRD patients was 70,211 at the end of 2012, which included 48,531 hemodialysis (HD) patients, 7,552 peritoneal dialysis (PD) patients, and 14,128 functioning kidney transplant (KT) patients. The prevalence of ESRD was 1,353.3 patients per million population (PMP), and the distribution of renal replacement therapy among ESRD patients was as follows: HD, 69.1%; PD, 10.8%; and KT, 20.2%. The number of new ESRD patients in 2012 was 11,742 (HD, 8,811; PD, 923; and KT, 1,738; the incidence rate was 221.1 PMP). The primary causes of ESRD were diabetic nephropathy (50.6%), hypertensive nephrosclerosis (18.5%), and chronic glomerulonephritis (18.1%). The mean urea reduction ratio was 67.9% in male and 74.1% in female HD patients. The mean Kt/V was 1.382 in male and 1.652 in female HD patients. The 5-year survival rates of male and female dialysis patients were 70.6% and 73.5%, respectively.

Clinical characteristics of acute renal failure with severe loin pain and patchy renal vasoconstriction

BACKGROUND: Acute renal failure (ARF) with severe loin pain and patchy renal vasoconstriction (PRV) is a syndrome presenting with sudden loin pain after anaerobic exercise. We aimed to investigate the clinical characteristics and the efficacy of diagnostic imaging studies of patients with this syndrome. METHODS: We retrospectively selected 17 patients with ARF accompanied by loin or abdominal pain who showed multiple patchy wedge-shaped delayed contrast enhancements on a computerized tomography scan. Information about the clinical characteristics, including the nature of pain and combined symptoms, suspected causes, such as exercise, drug or alcohol intake, and renal hypouricemia, and the results of laboratory and imaging tests were gathered. RESULTS: The mean age of patients with episodes of ARF accompanied by loin pain was 23.0+/-6.5 (range 16-35) years old. Pain was mainly located in the loin (70.6%) or abdominal area (76.5%) and continued for approximately 3.5+/-4.0 days. Exercise was suspected as a primary cause of disease in 12 (70.6%) patients. Maximal serum creatinine was 5.42+/-3.16 (1.4-12.1) mg/dL 3.1+/-1.8 (1-7) days after the onset of pain. The peak level of serum uric acid was 9.41+/-2.91 (6.0-15.8) mg/dL. All of the patients recovered to near-normal renal function, and one patient showed hypouricemia after recovery. CONCLUSION: ARF with severe loin pain and PRV can present with loin or abdominal pain, even without a history of anaerobic exercise. Careful history taking and appropriate imaging studies are critical in the diagnosis and management of this syndrome.

The effect of depression and health-related quality of life on the outcome of hemodialysis patients

BACKGROUND: In hemodialysis (HD) patients, traditional risk factors cannot explain all of the mortality and morbidity. This study was designed to investigate the effect of depression and health-related quality of life (HRQOL) on prognosis in maintenance HD patients. METHODS: In February 2008, the Beck's Depression Inventory and the Kidney Dialysis Quality of Life-Short Form were utilized to measure depression and HRQOL. Until February 2011, the mortality, cardiovascular events, infection, and hospitalization were investigated, retrospectively. RESULTS: Among the 166 patients, the 3-year cumulative survival rate was 88.8%, and the depression did not affect survival (depression vs. nondepression: 91.8% vs. 87.2%, P=0.437). The upper tertiles in physical component summary (PCS) were correlated with lower mortality (OR, 0.12; P=0.05) and fewer cardiovascular events (OR, 0.09; P=0.024) than the lower tertiles. The upper tertiles in kidney disease component summary (KDCS) were associated with less hospitalization than the lower tertiles (OR, 0.38; P=0.024). After adjusting for multiple variables including age, comorbidity index, and albumin, upper tertiles in PCS were correlated with fewer cardiovascular events than the lower tertiles (OR, 0.08; P=0.038). CONCLUSION: The cross-sectional survey of whether HD patients had depression was not significantly associated with mortality and morbidity. HRQOL was correlated with mortality, cardiovascular events and hospitalization.

Clinical Parameters to Determine the Optimal Timing of CRRT in Critically Ill Patients with Acute Kidney Injury / 대한신장학회지

PURPOSE: The aim of this study was to evaluate the clinical parameters to determine the optimal time for continuous renal replacement therapy (CRRT) in critically ill patients with severe acute kidney injury (AKI). METHODS: A single center retrospective study was performed using data from 166 AKI patients who received CRRT in intensive care unit (ICU) between October 2007 and January 2010. We compared mortality rate at 90 days after the initiation of CRRT, ICU-free and CRRT-free days between "early CRRT" and "late CRRT" groups stratified by blood urea nitrogen (BUN), serum creatinine, urine output and RIFLE criteria. RESULTS: The 90-day mortality rate was significantly lower in the early group compared with the late group when stratified by median value of BUN at the start of CRRT and mean hourly urine output during 6 h, 12 h, and 24 h before CRRT. In addition, the 90-day mortality rate was also significantly lower in patients who received CRRT in the "injury" stage of RIFLE criteria compared with those in "failure" or "loss" stage. ICU-free and CRRT-free days during the first 28 days were significantly longer in the early group when stratified by median level of BUN. However, in terms of creatinine, ICU-free and CRRT-free days were significantly shorter in the early group compared with the late group. CRRT-free days during the first 28 days were also longer in early group stratified by median value of mean hourly urine output during 6 h, 12 h before CRRT. After adjusting for covariates, 90-day mortality was independently lower in the early group defined by median level of BUN (OR=1.65 (1.10-2.47), p=0.015) and mean hourly urine output during 12h before CRRT (OR=1.56 (1.05-2.33), p=0.027). CONCLUSION: Our data suggest that early CRRT may have a survival benefit in critically ill patients with severe AKI, and BUN and urine output at the initiation of CRRT may be important parameters to determine the optimal time for CRRT.

How Long Should We Monitor the Patient for Bleeding after Percutaneous Renal Biopsy? / 대한신장학회지

PURPOSE: Percutaneous renal biopsy (PRB) may become complicated by serious bleeding. Overnight observation after renal biopsy is a standard safety strategy. Although it was recently reported that outpatient observation is safe, appropriate observation time after the renal biopsy is still in debate. We evaluated prospectively the incidence, onset time and risk factors of hemorrhagic complications to determine the optimal duration of observation after PRB. METHODS: We enrolled 100 patients who underwent renal biopsy from October 2009 to April 2010 using the standard strategy. The biopsy was performed by two experienced nephrologists using 16-gauge spring-loaded biopsy gun under real-time ultrasound guidance. Serial color Doppler ultrasound was done immediately, 8 hours, 24 hours and 1 week after the PRB. RESULTS: The 32 patients experienced hemorrhagic complications (32.0%, 10 with gross hematuria, 26 with hematoma, and 4 with both), and 1 major complication occurred 3 days after PRB. Baseline serum creatinine of the patient with the major complication was 6.0 mg/dL. Serum creatinine and BMI were higher in complication group (p<0.05). Number of needle passes, blood pressure, and degree of edema and proteinuria were not related to the complication. In multivariate analysis, serum creatinine was the only significant risk factor of complication (p=0.007). Hemorrhagic complications developed in 9 patients (28.1%) between 8 and 24 hours after PRB, all of which were minor. CONCLUSION: The 8 hours' observation time after renal biopsy may be deemed appropriate for stable patients with normal creatinine.

Clinicopathologic Characteristics of C1q nephropathy / 대한신장학회지

PURPOSE: C1q nephropathy (C1qN) is a rare glomerulonephritis characterized by mesangial deposits, predominantly C1q, without the evidence of systemic lupus erythematosus (SLE). It showed various clinical courses, however, the clinicopathologic features of C1qN have not been well defined as yet. METHODS: We retrospectively reviewed the clinicopathologic features of 11 patients (0.8%) diagnosed as C1qN among 1,403 patients aged > or = 18 years who had undergone renal biopsy due to primary glomerular disease from Jan. 2000 to Jan. 2009. Diagnostic criteria of C1qN were as follows; 1) the presence of dominant or co-dominant immunofluorescence staining for C1q in the mesangium, 2) corresponding mesangial dense deposit by electron microscopy, and 3) lack of clinical evidence of SLE. RESULTS: The male-to-female ratio was 6:5 and their mean age was 41.1+/-22.6 yrs (range, 19-69 yrs). Eight patients presented with urinary abnormalities and three with nephrotic syndrome. At the time of biopsy, three patients had hypertension. The mean value of 24-hour urine protein was 4.4+/-5.5 g/day (range, 0.5-18.5 g/day). On light microscopy, normal glomerular architecture (4/11) and segmental sclerosis (7/11) were observed. Complete or partial remission was achieved in six of the seven patients treated with immunosuppressive agents (steroid and/or immunosuppressants). Among these patients, two using steroid monotherapy had relapsed. The mean follow-up duration was 14+/-11 months (range, 2-31 months) and renal function deterioration was observed in three patients. CONCLUSION: C1qN showed various clinical manifestations and prognosis. Therefore, additional studies are needed to fully define the clinicopathologic features.

A Case of Pulmonary Adenocarcinoma Developed on a Previous Lesion from Microscopic Polyangiitis / 대한신장학회지

This report examines a patient with pulmonary adenocarcinoma that developed on a previous lesion from microscopic polyangiitis. A 59-year-old woman had been diagnosed with microscopic polyangiitis in October of 1988 based on her clinical symptoms and serological tests, which were positive for anti-neutrophil cytoplasmic antibodies. Her glomerulonephritis had been well controlled with low-dose prednisolone. She presented in October of 2005 with vague chest discomfort and dyspnea on exertion. Physical examination was unremarkable. A non-contrast computed tomography (CT) scan of the chest showed patch ground-glass opacity at the right lower lobe of the lung. Because we did not believe the lesion to be a definite malignancy, we decided to follow up with chest images over a short interval. During the 18 months following the images, the lesion did not change. However, the opacity of the lesion increased slightly over the last two months, and a non-contrast CT scan of the chest was therefore performed. A CT scan showed persistent ground-glass opacity with a slightly solid portion. To diagnose the previous finding and possibly to provide treatment, a right lower lobectomy of the lung via video-assisted thoracoscopic surgery was performed. The pathologic review of the resected lung revealed an adenocarcinoma, stage pT1N0. After one year, fluorodeoxyglucose positron emission tomography was performed, and no evidence of a recurrent malignancy was found.

2 Cases of Severe Hyperchloremic Metabolic Acidosis after Orthotopic Neobladder Replacement and Augmentation Enterocystoplasty / 대한신장학회지

The use of intestinal segments in the reconstruction and plasty of urinary bladder for malignant or nonmalignant conditions is widely accepted. Metabolic derangements including hyperchloremic metabolic acidosis and malabsorption of lipid may occur after surgery. Main pathophysiology of hyperchloremic metabolic acidosis is the exchange of urinary chloride with luminal bicarbonate and duration of urine in contact with the intestinal mucosa can affect the severity of metabolic acidosis. We experienced two cases of severe hyperchloremic metabolic acidosis which developed in patients with chronic kidney disease, urinary tract infection and orthotopic neobladder or augmentation enterocystoplasty for the treatment of bladder cancer and neurogenic bladder, respectively.

Ectopic ACTH Syndrome and Severe Hypokalemia Associated with Suspicious Pancreatic Malignancy: A Case Report / 대한신장학회지

A 72-year-old woman had a 1-month history of general weakness. Previously, after rectal cancer was treated with a low anterior resection, 12 cycles of adjuvant chemotherapy with 5-fluorouracil plus leucovorin was undergone. Follow-up examination showed no evidence of recurrence. However, she suffered from general weakness attributable to hypokalemia, which was refractory to potassium replacement therapy. After further work-up of the hypokalemia, Cushing's syndrome and ectopic adrenocorticotropic hormone (ACTH) syndrome were diagnosed from the laboratory findings that included a markedly elevated level of 24-hour urine-free cortisol. Several imaging studies revealed masses of the pancreas and other organs, which was more likely to be pancreatic cancer. This case is interesting in that cancerous lesions were identified during work-up of hypokalemia.

Improvement in Erythropoieis-stimulating Agent-induced Pure Red-cell Aplasia by Introduction of Darbepoetin-alpha When the Anti-erythropoietin Antibody Titer Declines Spontaneously

Anti-erythropoietin antibodies usually cross-react with all kinds of recombinant erythropoietins; therefore, erythropoiesis-stimulating agent (ESA)-induced pure red-cell aplasia (PRCA) is not rescued by different ESAs. Here, we present a case of ESA-induced PRCA in a 36-yr-old woman with chronic kidney disease, whose anemic condition improved following reintroduction of darbepoetin-alpha. The patient developed progressive, severe anemia after the use of erythropoietin-alpha. As the anemia did not improve after the administration of either other erythropoietin-alpha products or erythropoietin-beta, all ESAs were discontinued. Oxymetholone therapy failed to improve the transfusion-dependent anemia and a rechallenge with ESAs continuously failed to obtain a sustained response. However, her anemia improved following reintroduction of darbepoetin-alpha at 3 yr after the initial diagnosis. Interestingly, anti-erythropoietin antibodies were still detectable, although their concentration was too low for titration. In conclusion, darbepoetin-alpha can improve ESA-induced PRCA when the anti-erythropoietin antibody titer declines and its neutralizing capacity is lost.

High Dose Vitamin D3 Attenuates the Hypocalciuric Effect of Thiazide in Hypercalciuric Rats

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-D(28K), 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.