Evaluating the Safety and effectivenesS in adult KorEaN patients treated with Tolvaptan for management ofautosomal domInAnt poLycystic kidney disease (ESSENTIAL): short-term outcomes during the titration period

Tolvaptan reduces height-adjusted total kidney volume (htTKV) and renal function decline in autosomal dominant polycystic kidney disease (ADPKD). This study was aimed at investigating the efficacy and safety of tolvaptan in Korean patients with ADPKD during the titration period. Methods: This study is a multicenter, single-arm, open-label phase 4 study. We enrolled 108 patients with ADPKD (age, 19–50 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and factors defined as indicative of rapid disease progression. After tolvaptan titration, we evaluated efficacy and side effects and assessed factors associated with the effects. Results: After titration for 4 weeks, eGFR and htTKV decreased by 6.4 ± 7.9 mL/min/1.73 m2 and 16 ± 45 mL/m, respectively. No serious adverse drug reactions were observed during the titration period. The greatest eGFR decline was observed in the first week, with a starting tolvaptan dose of 45 mg. Multivariate linear regression for htTKV decline showed that the greater the change in urine osmolality (Uosm), the greater the decrease in htTKV (β, 0.436; p = 0.009) in the 1D group stratified by the Mayo Clinic image classification. Higher baseline eGFR was related to a higher htTKV reduction rate in the 1E group (β, –0.642; p = 0.009). Conclusion: We observed short-term effects and safety during the tolvaptan titration period. The decline of htTKV can be predicted as a short-term effect of tolvaptan by observing Uosm changes from baseline to end of titration in 1D and baseline eGFR in 1E groups.

Development of objective indicators for quantitative analysis of sodium intake: the sodium to potassium ratio of second-void urine is correlated with 24-hour urinary sodium excretion

The pattern of choosing dialysis modality and related mortality outcomes in Korea: a national population-based study

BACKGROUND/AIMS: Since comorbidities are major determinants of modality choice, and also interact with dialysis modality on mortality outcomes, we examined the pattern of modality choice according to comorbidities and then evaluated how such choices affected mortality in incident dialysis patients. METHODS: We analyzed 32,280 incident dialysis patients in Korea. Patterns in initial dialysis choice were assessed by multivariate logistic regression analyses. Multivariate Poisson regression analyses were performed to evaluate the effects of interactions between comorbidities and dialysis modality on mortality and to quantify these interactions using the synergy factor. RESULTS: Prior histories of myocardial infarction (p = 0.031), diabetes (p = 0.001), and congestive heart failure (p = 0.003) were independent factors favoring the initiation with peritoneal dialysis (PD), but were associated with increased mortality with PD. In contrast, a history of cerebrovascular disease and 1-year increase in age favored initiation with hemodialysis (HD) and were related to a survival benefit with HD (p < 0.001, both). While favoring initiation with HD, having Medical Aid (p = 0.001) and male gender (p = 0.047) were related to increased mortality with HD. Furthermore, although the severity of comorbidities did not inf luence dialysis modality choice, mortality in incident PD patients was significantly higher compared to that in HD patients as the severity of comorbidities increased (p for trend < 0.001). CONCLUSIONS: Some comorbidities exerted independent effects on initial choice of dialysis modality, but this choice did not always lead to the best results. Further analyses of the pattern of choosing dialysis modality according to baseline comorbid conditions and related consequent mortality outcomes are needed.

Effect of Personalized Nutritional Counseling on the Nutritional Status of Hemodialysis Patients

This study set out to evaluate the impact of personalized nutritional counseling (PNC) on the nutritional status of hemodialysis (HD) patients. This was an intervention study for 10 months at 2 hospitals. Anthropometric, biochemical, dietary, and body composition parameters were measured at baseline and after 3 and 6 months of PNC. A total of 42 patients (23 men and 19 women) were included. Intake of dietary protein, serum albumin, and cholesterol levels had increased significantly from baseline to month 6 (p < 0.05). Among the bioelectrical impedance analysis (BIA) parameters, both the body cell mass (BCM) and the fat free mass (FFM) had significantly reduced at month 3 compared to baseline (p < 0.05). However, there was no difference between baseline and month 6. We assessed the nutritional status of the subjects using the malnutrition inflammation score (MIS), and divided them into an adequately nourished (AN) and a malnourished (MN) group at baseline. In the subgroup analysis, serum levels of albumin and cholesterol had increased significantly, particularly from baseline to month 6 in the MN group (p < 0.05). This study suggests that consecutive PNC contributed to the improvement of the protein intake, serum levels of albumin, cholesterol and to the delay of muscle wasting, which could also have a positive impact on the nutritional status, particularly in malnourished patients receiving HD treatment.

Association of Serotonin 1A Receptor Polymorphism with Variation in Health-Related Quality of Life in Korean Hemodialysis Patients

OBJECTIVE: Hemodialysis patients may have psychological distress and reduced quality of life (QoL) related to chronic physical health problems. Genetic polymorphisms associated with reduced QoL in hemodialysis patients. The aim of this study was to investigate the relationship between genetic polymorphisms and variation in health-related QoL in Korean hemodialysis patients. METHODS: The 36-item Short-Form Health Survey and the Korean Hospital Anxiety and Depression Scale were used to assess health-related QoL and psychological distress, respectively. Twenty hundred and five clinically stable patients from 6 hemodialysis centers have participated with informed consents. Sociodemographic factors, clinical factors, and genotypes of serotonin 1A receptor, brain-derived neurotrophic factors, and glucocorticoid receptor were assessed. Independent t-tests, correlation analyses, multiple regression analyses were performed for statistical analyses. RESULTS: The serotonin 1A receptor CC genotype group showed significantly higher physical and mental QoL levels than those with the GG/GC genotypes. In the final linear regression analysis, serotonin 1A receptor CC genotype was significantly associated with positive physical and mental QoL levels. CONCLUSION: ConclusionaaSerotonin 1A receptor polymorphism, as well as age and depression, were significantly associated with mental and physical QoL in hemodialysis patients. Functional activity in the serotonin receptor system may have a modulating effect on health-related QoL in hemodialysis patients.

Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial

BACKGROUND/AIMS: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. METHODS: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. RESULTS: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% +/- 26.1% (p < 0.001) in the regular-dose group and -21.1% +/- 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period. CONCLUSIONS: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.

Salt Sensitivity and Hypertension: A Paradigm Shift from Kidney Malfunction to Vascular Endothelial Dysfunction

Hypertension is a complex trait determined by both genetic and environmental factors and is a major public health problem due to its high prevalence and concomitant increase in the risk for cardiovascular disease. With the recent large increase of dietary salt intake in most developed countries, the prevalence of hypertension increases tremendously which is about 30% of the world population. There is substantial evidence that suggests some people can effectively excrete high dietary salt intake without an increase in arterial BP, and another people cannot excrete effectively without an increase in arterial BP. Salt sensitivity of BP refers to the BP responses for changes in dietary salt intake to produce meaningful BP increases or decreases. The underlying mechanisms that promote salt sensitivity are complex and range from genetic to environmental influences. The phenotype of salt sensitivity is therefore heterogeneous with multiple mechanisms that potentially link high salt intake to increases in blood pressure. Moreover, excess salt intake has functional and pathological effects on the vasculature that are independent of blood pressure. Epidemiologic data demonstrate the role of high dietary salt intake in mediating cardiovascular and renal morbidity and mortality. Almost five decades ago, Guyton and Coleman proposed that whenever arterial pressure is elevated, pressure natriuresis enhances the excretion of sodium and water until blood volume is reduced sufficiently to return arterial pressure to control values. According to this hypothesis, hypertension can develop only when something impairs the excretory ability of sodium in the kidney. However, recent studies suggest that nonosmotic salt accumulation in the skin interstitium and the endothelial dysfunction which might be caused by the deterioration of vascular endothelial glycocalyx layer (EGL) and the epithelial sodium channel on the endothelial luminal surface (EnNaC) also play an important role in nonosmotic storage of salt. These new concepts emphasize that sodium homeostasis and salt sensitivity seem to be related not only to the kidney malfunction but also to the endothelial dysfunction. Further investigations will be needed to assess the extent to which changes in the sodium buffering capacity of the skin interstitium and develop the treatment strategy for modulating the endothelial dysfunction.

High Water Intake and Progression of Chronic Kidney Diseases

Impact of water intake on the courses of chronic kidney and urinary tract diseases, such as urolithiasis, urinary tract infections, chronic kidney diseases (CKD), autosomal dominant polycystic kidney diseases and bladder cancer, has recently been studied. It still remains controversial whether increased water intake slows the progression of CKD or not. However, high water intake suppresses plasma levels of arginine vasopressin (AVP), which is expected to be beneficial for the preservation of the kidney function. Previous studies suggest that water intake suppresses plasma levels of AVP, and high levels of AVP have been suggested to play deleterious roles in animal models of kidney disease. Moreover, recent epidemic of CKD of unknown origin, which was supposed to be related to the insufficient water intake and chronic volume depletion, has been reported in Central America, further suggesting that the suppression of AVP by sustained water intake might be beneficial in this CKD population. Indeed, the data from recent studies were consistent with the view that high water intake is associated with slower progression of CKD. However, contradictory findings also exist. The intriguing effects of increased urine volume in preserving the glomerular filtration rate in human patients with CKD require more large and well-designed randomized prospective clinical trials.

Epidermal Proteinase-Activated Receptor-2 Expression is Increased in End-Stage Renal Disease Patients with Pruritus: A Pilot Study

Uremic pruritus is a common problem in patients with end-stage renal disease (ESRD), but the underlying mechanisms are not yet fully understood. We aimed to investigate the association between severity of uremic pruritus and cutaneous serine protease activity, as well as proteinase-activated receptor-2 (PAR-2) expression. Twelve ESRD patients with pruritus, 4 ESRD patients without pruritus, and 6 healthy controls were enrolled. Skin biopsies were obtained from the abdomen. Protease activity and PAR-2 expression in the epidermis were examined by in situ zymography and confocal laser microscopy, respectively. All ESRD patients presented more pronounced cutaneous protease activity compared with that in healthy controls. The skin samples from the patients with pruritus showed higher protease activity than either nonpruritic ESRD patients or healthy controls. The epidermis in all samples of ESRD patients presented higher immunoreactivity against PAR-2 versus those of healthy controls. In addition, correlation analysis between PAR-2 expression and VAS pruritus scores showed a significant positive correlation. Our data suggests that levels of serine protease and PAR-2 expression could play important roles in the pathogenesis of uremic pruritus.

How do We Manage Coronary Artery Disease in Patients with CKD and ESRD?

Chronic kidney disease (CKD) has been shown to be an independent risk factor for cardiovascular events. In addition, patients with pre-dialysis CKD appear to be more likely to die of heart disease than of kidney disease. CKD accelerates coronary artery atherosclerosis by several mechanisms, notably hypertension and dyslipidemia, both of which are known risk factors for coronary artery disease. In addition, CKD alters calcium and phosphorus homeostasis, resulting in hypercalcemia and vascular calcification, including the coronary arteries. Mortality of patients on long-term dialysis therapy is high, with age-adjusted mortality rates of about 25% annually. Because the majority of deaths are caused by cardiovascular disease, routine cardiac catheterization of new dialysis patients was proposed as a means of improving the identification and treatment of high-risk patients. However, clinicians may be uncomfortable exposing asymptomatic patients to such invasive procedures like cardiac catheterization, thus noninvasive cardiac risk stratification was investigated widely as a more palatable alternative to routine diagnostic catheterization. The effective management of coronary artery disease is of paramount importance in uremic patients. The applicability of diagnostic, preventive, and treatment modalities developed in nonuremic populations to patients with kidney failure cannot necessarily be extrapolated from clinical studies in non-kidney failure populations. Noninvasive diagnostic testing in uremic patients is less accurate than in nonuremic populations. Initial data suggest that dobutamine echocardiography may be the preferred diagnostic method. PCI with stenting is a less favorable alternative to CABG, however, it has a faster recovery time, reduced invasiveness, and no overall mortality difference in nondiabetic and non-CKD patients compared with CABG. CABG is associated with reduced repeat revascularizations, greater relief of angina, and increased long term survival. However, CABG is associated with a higher incidence of post-operative risks. The treatment chosen for each patient should be an individualized decision based upon numerous risk factors. CKD is associated with higher rates of CAD, with 44% of all-cause mortality attributable to cardiac disease and about 20% from acute MI. Optimal treatment including aggressive lifestyle modifications and concomitant medical therapy should be implemented in all patients to maximize benefits from either PCI or CABG. Future prospective randomized controlled trials with newer second or third generation DES and bioabsorbable DES are necessary to determine if PCI may be non-inferior to CABG in the future.

Asymptomatic renal pseudoaneurysm after percutaneous renal biopsy

A 37-year-old man was referred to Division of Nephrology for a new renal cystic lesion that was found on ultrasonography. Four years prior to presentation, a percutaneous renal biopsy had been performed. Computed tomography scan showed a 4.4-cm-sized renal artery pseudoaneurysm in the left kidney. Selective renal angiography revealed a pseudoaneurysm in the left lower pole of the kidney. The renal pseudoaneurysmwas successfully embolized with coil. Follow-up Doppler ultrasonography showed no internal blood flow into the aneurysmal sac. His renal function remained stable after coil embolization.

Sulodexide in IgA nephropathy

No abstract available.

Sulodexide in IgA nephropathy

No abstract available.

Asymptomatic renal pseudoaneurysm after percutaneous renal biopsy Volume 32, Issue 2, June 2013, pp. 87-89

No abstract available.

Serum osteoprotegerin is associated with vascular stiffness and the onset of new cardiovascular events in hemodialysis patients

BACKGROUND/AIMS: Osteoprotegerin (OPG) and fetuin-A are vascular calcification regulators that may be related to high cardiovascular (CV) mortality in hemodialysis (HD) patients. We evaluated the relationship between OPG, fetuin-A, and pulse wave velocity (PWV), a marker of vascular stiffness, and determined whether OPG and fetuin-A were independent predictors of CV events in HD patients. METHODS: We conducted a prospective observational study in 97 HD patients. OPG and fetuin-A were measured at baseline and arterial stiffness was evaluated by PWV. All patients were stratified into tertiles according to serum OPG levels. RESULTS: A significant trend was observed across increasing serum OPG concentration tertiles for age, HD duration, systolic blood pressure, cholesterol, triglycerides, and PWV. Multiple linear regression analysis revealed that diabetes (beta = 0.430, p = 0.000) and OPG levels (beta = 0.308, p = 0.003) were independently associated with PWV. The frequency of new CV events was significantly higher in the upper OPG tertiles compared with those in the lower OPG tertiles. In Cox proportional hazards analysis, upper tertiles of OPG levels were significantly associated with CV events (hazard ratio = 4.536, p = 0.011). CONCLUSIONS: Serum OPG, but not fetuin-A, levels were closely associated with increased vascular stiffness, and higher OPG levels may be independent predictors of new CV events in HD patients.

A Case of Severe Metabolic Acidosis Associated with Sodium Hypochlorite (Bleach) Poisoning Treated by Hemodialysis / 대한내과학회지

Sodium hypochlorite (NaOCl) is commonly used as a disinfectant or bleaching agent. The ingestion of household bleach is often benign, with minimal irritating effect on the mucosa. Occasionally, however, it can be life-threatening. Here, we report an unusual case of acute poisoning involving household bleach with a near-fatal outcome that was treated with intense hemodialysis. A 42-year-old woman presented to the emergency room after ingesting 1 liter of 5% household bleach. Ten hours later, her metabolic acidosis, hypernatremia, hyperchloremia, and renal failure deteriorated gradually, despite aggressive medical treatment. Rapid, effective correction of the metabolic acidosis and electrolytes imbalance was needed and hemodialysis was performed immediately. After 3 days of dialysis, the laboratory imbalance was completely corrected.

Effects of Lowering Dialysate Calcium Concentrations on Arterial Stiffness in Patients Undergoing Hemodialysis

BACKGROUND/AIMS: We assessed changes in hemodynamic and arterial stiffness parameters following reductions of dialysate calcium concentrations in patients undergoing hemodialysis. METHODS: In this prospective study, 20 patients on maintenance hemodialysis (10 females, 10 males) with dialysate calcium concentrations of 1.75 mmol/L were enrolled. At the start of the study, the dialysate calcium level was lowered to 1.50 mmol/L. Serial changes in biochemical, hemodynamic, and arterial stiffness parameters, including pulse wave velocity (PWV) and augmentation index (AIx), were assessed every 2 months for 6 months. We also examined changes in the calcification-inhibitory protein, serum fetuin-A. RESULTS: During the 6-month study period, serum total calcium and ionized calcium decreased consistently (9.5 +/- 1.0 to 9.0 +/- 0.7, p = 0.002 vs. 1.3 +/- 0.1 to 1.1 +/- 0.1, p = 0.035). Although no apparent changes in blood pressure were observed, heart-femoral PWW (hf-PWV) and AIx showed significant improvement (p = 0.012, 0.043, respectively). Repeated-measures ANOVA indicated a significant effect of lowering dialysate calcium on hf-PWV (F = 4.58, p = 0.004) and AIx (F = 2.55, p = 0.049). Accompanying the change in serum calcium, serum fetuin-A levels significantly increased (95.8 +/- 45.8 pmol/mL at baseline to 124.9 +/- 82.2 pmol/mL at 6 months, p = 0.043). CONCLUSIONS: Lowering dialysate calcium concentration significantly improved arterial stiffness parameters, which may have been associated with upregulation of serum fetuin-A.

Severe Symptomatic Hyponatremia Caused by Low Dose Oral Cyclophosphamide: A Case Report / 대한신장학회지

Cyclophosphamide (CY), an alkylating agent, is frequently used in the treatment of various autoimmune disorders and malignancies. Acute hyponatremia is a well-known side effect of moderate to high dose intravenous CY treatment, but is rare in patients treated with low dose intravenous CY. We report the case of a severe symptomatic hyponatremia in a 68-year-old woman with renal impairment who was treated with oral CY (100 mg/day) for anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN). This case demonstrates that even oral CY could be associated with life threatening acute hyponatremia and should be used with caution.

Rhabdomyolysis-Induced Acute Kidney Injury Associated with Posterior Reversible Encephalopathy Syndrome / 대한신장학회지

Posterior reversible encephalopathy syndrome (PRES) is characterized by altered mental status, headache, vomiting, visual loss, seizure and reversible posterior subcortical white matter and cortex edema in brain image studies. It is often associated with malignant hypertension and immunosuppression. We present a 30-year-old male with PRES. He was admitted to our hospital with rhabdomyolysis and acute kidney injury (AKI). During the hospital course, he developed acute malignant hypertension accompanied by visual loss and generalized seizure. Brain MRI demonstrated increased signal intensity with gyral swelling in cerebellar hemisphere, parieto-occipital cortex, and subcortical white matter area. Following aggressive blood pressure control and hemodialysis the patient recovered fully without any neurologic or visual complications. We report a case of PRES associated with AKI due to rhabdomyolysis.

Serum Adiponectin as a Predictor for Cardiovascular Outcomes in Non-Diabetic End-Stage Renal Disease Patients / 대한신장학회지

PURPOSE: Adiponectin (ADPN) has been known to protect against cardiovascular disease (CVD) in metabolic syndrome with normal renal function for its anti-inflammatory and anti-atherogenic property. However, it is still unclear whether ADPN is associated with cardiovascular outcomes in end-stage renal disease (ESRD) patients. METHODS: This study included 80 non-diabetic ESRD patients [mean age, 52.8+/-13.7 years; dialysis duration, 67.1+/-52.0 months; hemodialysis (HD), 35 pts; peritoneal dialysis (PD), 45 pts] who survived for more than 3 months after the start of dialysis, and serum ADPN levels were measured at the beginning of the study. We conducted a longitudinal follow-up to evaluate the association of serum ADPN level with cardiovascular outcomes for 29.3+/-6.7 months. RESULTS: ADPN was inversely correlated with fasting serum insulin (r=-0.309, p=0.006) and HOMA-IR (r=-0.321, p=0.004) in ESRD patients. In a multiple linear regression analysis adjusted for age, gender, waist to hip ratio (WHR), and HDL-cholesterol, HOMA-IR (beta=-0.880, p=0.041) was an independent factor associated with serum ADPN level. Kaplan-Meier analysis revealed that patients with higher ADPN levels (> or =15.8 microgram/mL) had a significantly higher survival rate compared with lowers (<15.8 microgram/mL) (p=0.032). Cox proportional hazard model adjusted for age, WHR, creatinine, CRP, and previous CVD history revealed that serum ADPN level (HR, 0.899; 95% CI, 0.818-0.987; p=0.026) was an independent determinant of cardiovascular outcomes. CONCLUSION: These findings suggest that lower ADPN levels independently predict cardiovascular events in non-diabetic ESRD patients.