Recent advances in dialysis and a multidisciplinary approach to pregnant patients with advanced chronic kidney disease provide a better outcome. A 38-yr-old female with autosomal dominant polycystic kidney disease (ADPKD) became pregnant. She was undergoing hemodialysis (HD) and her kidneys were massively enlarged, posing a risk of intrauterine fetal growth restriction. By means of intensive HD and optimal management of anemia, pregnancy was successfully maintained until vaginal delivery at 34.5 weeks of gestation. We discuss the special considerations involved in managing our patient with regard to the underlying ADPKD and its influence on pregnancy.
Pregnancy; Renal Dialysis; Polycystic Kidney, Autosomal Dominant
Polycystic liver is the most common extra-renal manifestation associated with autosomal dominant polycystic kidney disease (ADPKD), comprising up to 80% of all features. Patients with polycystic liver often suffer from abdominal discomfort, dyspepsia, or dyspnea; however, there have been few ways to relieve their symptoms effectively and safely. Therefore, we tried transcatheter arterial embolization (TAE), which has been used in treating hepatocellular carcinoma. We enrolled four patients with ADPKD in Seoul National University Hospital, suffering from enlarged polycystic liver. We embolized the hepatic arteries supplying the dominant hepatic segments replaced by cysts using polyvinyl alcohol particles and micro-coils. The patients were evaluated 12 months after embolization for the change in both liver and cyst volumes. Among four patients, one patient was lost in follow up and 3 patients were included in the analysis. Both liver (33%; 10%) and cyst volume (47.7%; 11.4%) substantially decreased in two patients. Common adverse events were fever, epigastric pain, nausea, and vomiting. We suggest that TAE is effective and safe in treating symptomatic polycystic liver in selected ADPKD patients.
Polycystic Kidney, Autosomal Dominant; Embolization, Therapeutic
Acute kidney injury; Sarcoidosis; Subcutaneous tissue
The progression and complications of chronic kidney disease should differ depending on the cause (C), glomerular filtration rate category (G), and albuminuria (A). The KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease), which is a prospective cohort study, enrolls subjects with chronic kidney disease stages 1 to 5 (predialysis).
Nine nephrology centers in major university hospitals throughout Korea will enroll approximately 2,450 adults with chronic kidney disease over a 5-year period from 2011 to 2015. The participating individuals will be monitored for approximately 10 years until death or until end-stage renal disease occurs. The subjects will be classified into subgroups based on the following specific causes of chronic kidney disease: glomerulonephritis, diabetic nephropathy, hypertensive nephropathy, polycystic kidney disease, and others. The eligible subjects will be evaluated at baseline for socio-demographic information, detailed personal/family history, office BP, quality of life, and health behaviors. After enrollment in the study, thorough assessments, including laboratory tests, cardiac evaluation and radiologic imaging, will be performed according to the standardized protocol. The biospecimen samples will be collected regularly. A renal event is defined by >50% decrease in estimated GFR (eGFR) from the baseline values, doubling of serum creatinine, or end-stage renal disease. The primary composite outcome consists of renal events, cardiovascular events, and death. As of September 2013, 1,470 adult chronic kidney disease subjects were enrolled in the study, including 543 subjects with glomerulonephritis, 317 with diabetic nephropathy, 294 with hypertensive nephropathy and 249 with polycystic kidney disease.
As the first large-scale chronic kidney disease cohort study to be established and maintained longitudinally for up to 10 years, the KNOW-CKD will help to clarify the natural course, complication profiles, and risk factors of Asian populations with chronic kidney disease.
No. NCT01630486 at http://www.clinicaltrials.gov.
KNOW-CKD; Chronic kidney disease; Cohort; Etiology; Progression; Complication; Natural course
The role of hyperuricemia in disease progression of autosomal dominant polycystic kidney disease (ADPKD) has not been defined well. We investigated the association of serum uric acid (sUA) with renal function and the effect of hypouricemic treatment on the rate of renal function decline.
This is a single-center, retrospective, observational cohort study. A total of 365 patients with ADPKD who had estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2 and who were followed up for > 1 year were included in our analysis. Hyperuricemia was defined by a sUA level of ≥ 7.0 mg/dL in male and ≥ 6.0 mg/dL in female or when hypouricemic medications were prescribed.
Hyperuricemia was associated with reduced initial eGFR, independent of age, sex, hypertension, albuminuria, and total kidney volume. During a median follow-up period of over 6 years, patients with hyperuricemia showed a faster annual decline in eGFR (−6.3% per year vs. −0.9% per year, p = 0.008). However, after adjusting for age, sex, hypertension and initial eGFR, sUA was no longer associated with either annual eGFR decline or the development of ESRD. Among 53 patients who received hypouricemic treatment, the annual eGFR decline appeared to be attenuated after hypouricemic treatment (pretreatment vs. posttreatment: −5.3 ± 8. 2 vs. 0.2 ± 6.2 mL/min/1.73 m2 per year, p = 0.001 by Wilcoxon signed-rank test).
Although hyperuricemia was associated with reduced eGFR, it was not an independent factor for renal progression in ADPKD. However, the correction of hyperuricemia may attenuate renal function decline in some patients with mild renal insufficiency.
Glomerular filtration rate; Hyperuricemia; Polycystic kidney; Autosomal dominant; Uric acid
Evidence is emerging that exposure to persistent organic pollutants (POPs) is a risk factor for obesity‐related diseases and for diabetes mellitus (DM). We found that POPs could be measured by a cell‐based arylhydrocarbon receptor (AhR)‐dependent reporter assay. We tested if serum AhR transactivating (AHRT) activities are a risk factor for diabetic nephropathy in people with type 2 diabetes.
Materials and Methods
We enrolled diabetic patients with normoalbuminuria (n = 36), microalbuminuria (n = 29), macroalbuminuria (n = 8) and end‐stage renal disease (n = 31). Sera were tested for their AHRT activities, which were standardized by an AhR ligand, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) and expressed as TCDD equivalents (TCDDeq pmol/L).
Mean serum AHRT activities were higher in patients with microalbuminuria (40.1 ± 7.1 pmol/L), macroalbuminuria (37.4 ± 5.5 pmol/L) and end‐stage renal disease (59.1 ± 20.0 pmol/L) than in subjects with normoalbuminuria (12.7 ± 5.4 pmol/L; P < 0.05 for all comparisons). Serum AhR ligands showed a correlation with estimated glomerular filtration rate (eGFR; r = −0.663, P < 0.001), serum creatinine level (r = 0.635, P < 0.001), systolic blood pressure (r = 0.223, P = 0.026), glycated hemoglobim (r = 0.339, P < 0.001) and diabetic duration (r = 0.394, P < 0.001). In a multiple regression analysis, diabetic nephropathy was found to be an independent risk factor for higher AHRT activity after controlling for the confounding factors.
The present findings suggest serum AHRT activity, thus serum AhR ligands, is a risk factor for diabetic nephropathy. Further studies are required to clarify if an accumulation of POPs in the body is causally related to diabetic nephropathy.
Aryl hydrocarbon receptor ligands; Diabetic nephropathy; Persistent organic pollutants
Transparent flexible fluorine-doped indium zinc oxide (IZO:F) thin-film transistors (TFTs) were demonstrated using the spin-coating method of the metal fluoride precursor aqueous solution with annealing at 200°C for 2 hrs on polyethylene naphthalate films. The proposed thermal evolution mechanism of metal fluoride aqueous precursor solution examined by thermogravimetric analysis and Raman spectroscopy can easily explain oxide formation. The chemical composition analysed by XPS confirms that the fluorine was doped in the thin films annealed below 250°C. In the IZO:F thin films, a doped fluorine atom substitutes for an oxygen atom generating a free electron or occupies an oxygen vacancy site eliminating an electron trap site. These dual roles of the doped fluorine can enhance the mobility and improve the gate bias stability of the TFTs. Therefore, the transparent flexible IZO:F TFT shows a high mobility of up to 4.1 cm2/V·s and stable characteristics under the various gate bias and temperature stresses.
A 62-yr-old woman with an autosomal dominant polycystic kidney disease (ADPKD) was admitted to our hospital for further evaluation of intermittent fever, nausea and left flank discomfort. The computed tomography (CT) scan revealed a gas-forming, infectious cyst of approximately 8.1 cm in size in left kidney lower pole. Escherichia coli was identified from the cyst fluid culture examination. Her symptoms improved only after the concomitant use of intravenous ciprofloxacin and an intracystic irrigation of ciprofloxacin through a percutaneous cystostomy drainage. Our case presents the successfully treated emphysematous cyst infection with combination of intravenous antibiotics and intracystic antibiotic therapy instead of surgical management.
Autosomal Dominant Polycystic Kidney Disease; Escherichia coli; Emphysematous
Elevated serum level of fibroblast growth factor-23 (FGF23) is associated with adverse outcomes in dialyzed patients.
The CUPID study compared the efficacy of a cinacalcet-based regimen with conventional care (vitamin D and P binders) for achieving the stringent NKF-K/DOQI targets for peritoneal dialysis (PD) patients. Additionally, we analyzed change in FGF23 levels between two treatments to explore the cinacalcet effect in lowering FGF23.
Multicenter, open-labeled, randomized controlled study.
Seven university-affiliated hospitals in Korea.
Overall, 66 peritoneal dialysis patients were enrolled.
Sixty six patients were randomly assigned to treatment with either cinacalcet + oral vitamin D (cinacalcet group, n = 33) or oral vitamin D alone (control group, n = 33) to achieve K/DOQI targets. CUPID included a 4-week screening for vitamin D washout, a 12-week dose-titration, and a 4-week assessment phases. We calculated mean values of iPTH, Ca, P, Ca x P, during assessment phase and final FGF23 to assess the outcome.
Main outcome measures
Achievement of >30% reduction of iPTH from baseline (primary) and FGF23 reduction (secondary).
72.7% (n = 24) of the cinacalcet group and 93.9% (n = 31) of the control group completed the study. Cinacalcet group received 30.2 ± 18.0 mg/day of cinacalcet and 0.13 ± 0.32 μg/d oral vitamin D (P < 0.001 vs. control with 0.27 ± 0.18 μg/d vitamin D). The proportion of patients who reached the primary endpoint was not statistically different (48.5% vs. 51.5%, cinacalcet vs. control, P = 1.000). After treatment, cinacalcet group experienced a significant reduction in FGF23 levels (median value from 3,960 to 2,325 RU/ml, P = 0.002), while an insignificant change was shown for control group (from 2,085 to 2,415 RU/ml). The percent change of FGF23 after treatment was also significantly different between the two groups (− 42.54% vs. 15.83%, P = 0.008). After adjustment, cinacalcet treatment was independently associated with the serum FGF23 reduction.
Cinacalcet treatment was independently associated with the reduction of FGF23 in our PD patients.
Controlled trials NCT01101113
Cinacalcet; Fibroblast growth factor 23; Peritoneal dialysis
Urinary tract infection (UTI) occurs in 30%-50% of individuals with autosomal dominant polycystic kidney disease (ADPKD). However, the clinical relevance of asymptomatic pyuria in ADPKD patients remains unknown.
We retrospectively reviewed medical records of 256 ADPKD patients who registered to the ADPKD clinic at Seoul National University Hospital from Aug 1999 to Aug 2010. We defined the asymptomatic pyuria as more than 5-9 white blood cells in high-power field with no related symptoms or signs of overt UTI. Patients were categorized into 2 groups depending on its duration and frequency: Group A included non-pyuria and transient pyuria patients; Group B included recurrent and persistent pyuria patients. The association between asymptomatic pyuria and both the development of overt UTI and the deterioration of renal function were examined.
With a mean follow-up duration of 65.3 months, 176 (68.8%) out of 256 patients experienced 681 episodes of asymptomatic pyuria and 50 episodes of UTI. The annual incidence of asymptomatic pyuria was 0.492 episodes/patient/year. The patients in group B showed female predominance (58.5% vs. 42.0%, P=0.01) and experienced an upper UTI more frequently (hazard ratio: 4.612, 95% confidence interval: 1.735-12.258; P=0.002, adjusted for gender and hypertension). The annual change in estimated glomerular filtration rate (ΔeGFR) was significantly larger in magnitude in group B than in group A (-2.7±4.56 vs. -1.17±5.8, respectively; P=0.01). Age and Group B found to be the independent variables for ΔeGFR and developing end-stage renal disease (16.0% vs. 4.3%, respectively; P=0.001).
Chronic asymptomatic pyuria may increase the risk of developing overt UTI and may contribute to declining renal function in ADPKD.
Polycystic kidney disease; Chronic renal failure; Glomerular filtration rate; Pyuria; Urinary tract infection
Renal failure is one of the most serious complications associated with autosomal dominant polycystic kidney disease (ADPKD). To date, early markers have failed to predict renal function deterioration at the early stages. This 1-year prospective study evaluated N-acetyl-β-D-glucosaminidase (NAG) as a new surrogate marker for renal function in ADPKD.
A total of 270 patients were enrolled in the study, and we measured urinary NAG, β2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) prospectively for 1 year to compare their predictive values for renal function.
Baseline urinary NAG/Cr was negatively correlated with estimated glomerular filtration rate (GFR) (r2 = 0.153, P < 0.001) and positively correlated with total kidney volume (TKV) (r2 = 0.113, P < 0.001). Among other biomarkers, urinary NAG/Cr better discriminated patients with decreased renal function from those with conserved renal function, showing the largest area under the curve (AUC 0.794). Immunohistochemical study revealed strong staining along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells. However, both single and repeated measurements of urinary NAG/Cr failed to predict renal function decline in 1 year.
Urinary NAG/Cr may be a useful surrogate marker for renal function in ADPKD patients.
Autosomal dominant polycystic kidney disease; Biomarkers; Renal function
Recent studies reported that early initiation of hemodialysis may increase mortality. However, studies that assessed the influence of early initiation of peritoneal dialysis (PD) yielded controversial results. In the present study, we evaluated the prognosis of early initiation of PD on the various outcomes of end stage renal failure patients by using propensity-score matching methods. Incident PD patients (n = 491) who started PD at SNU Hospital were enrolled. The patients were divided into 'early starters (n = 244)' and 'late starters (n = 247)' on the basis of the estimated glomerular filtration rate (eGFR) at the start of dialysis. The calculated propensity-score was used for one-to-one matching. After propensity-score-based matching (n = 136, for each group), no significant differences were observed in terms of all-cause mortality (P = 0.17), technique failure (P = 0.62), cardiovascular event (P = 0.96) and composite event (P = 0.86) between the early and late starters. Stratification analysis in the propensity-score quartiles (n = 491) exhibited no trend toward better or poorer survival in terms of all-cause mortality. In conclusion, early commencement of PD does not reduce the mortality risk and other outcomes. Although the recent guidelines suggest that initiation of dialysis at higher eGFR, physicians should not determine the time to initiate PD therapy simply rely on the eGFR alone.
Peritoneal Dialysis; End Stage Renal Failure; Dialysis Initiation; Propensity Score Match; Outcome; Survival
The pharmacokinetics (PK) of ceftazidime after intravenous (i.v.) administration during automated peritoneal dialysis (APD) and their dependence on peritoneal membrane transport are the targets of the present study. Eleven patients receiving a single i.v. dose of ceftazidime (15 mg/kg of body weight) (seven males, median [interquatile] age, 59 [36 to 62]) were recruited. Serum and dialysate samples were collected at the beginning, middle, and end of each of the five dwells during a 24-h period, with dwells 1, 2, and 3 using an automated cycler (designated on-cycler) and dwells 4 and 5 being manual exchanges (designated off-cycler), together with urine collection during the same period. Population PK analysis was employed to estimate the PK parameters. Peritoneal equilibration tests were performed for all patients, and correlations between peritoneal clearance (CLPD) for ceftazidime and dialysate-to-plasma ratios for creatinine (D/Pcr) were obtained using the Spearman's product correlation coefficient (ρ). Ceftazidime renal clearance (CLrenal) was 0.052 ml/min/kg, and CLPD was 0.063 ± 0.050 ml/min/kg. CLPD for on- and off-cycler were 0.071 and 0.058 ml/min/kg (P = 0.164), respectively. A significant correlation between CLPD and D/Pcr was observed, with one outlier excluded, suggesting that CLPD for ceftazidime during APD is dependent upon the peritoneal small-solute transport rate. A model prediction yielded adequate serum and dialysate concentrations of ceftazidime throughout a 24-h period for sensitive organisms (MIC, 8 μg/ml) by either i.v. (at 15 mg/kg) or intraperitoneal (i.p.; at 20 mg/kg) administration during off-cycler dwells. The present study suggests that the i.v. administration of ceftazidime at 15 mg/kg or i.p. administration of ceftazidime at 20 mg/kg during a long dwell every 24 h can be recommended for treating systemic or intraperitoneal infections of APD patients.
We report a case of central venous stenosis due to a structural deformity caused by a tuberculosis-destroyed lung in a 65-year-old woman. The patient presented with left facial edema. She had a history of pulmonary tuberculosis, and the chest X-ray revealed a collapsed left lung. Angiography showed leftward deviation of the innominate vein leading to kinking and stenosis of the internal jugular vein. Stent insertion improved her facial edema.
Venous insufficiency; Tuberculosis, pulmonary; Lung injury
Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder associated with bone marrow involvement of lymphoplasmacytic lymphoma (LPL) and an IgM monoclonal gammopathy. Generally B-lymphocytes in LPL do not express CD5 that is important for differential diagnosis of B-cell lymphoproliferative disorders. In WM, various renal diseases and type I cryoglobulinemia are well described separately, but cryoglobulinemic glomerulonephropathy is very rarely reported. A 61-yr-old woman complained of generalized edema, cyanosis of the extremities in cold weather, visual disturbance, and pancytopenia. Bone marrow and renal biopsy showed CD5+ expressing B-cells and cryoglobulinemic glomerulonephropathy. With the diagnosis of WM, she received cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and got complete remission. Here, we report a rare case of WM associated with unusual expression of CD5+ B-lymphocytes and cryoglobulinemic glomerulonephropathy, and emphasize the importance of the clinical features in differentiating CD5+ B-cell lymphoproliferative disorders.
Waldenstrom Macroglobulinemia; CD5+ Lymphoplasmacytic Lymphoma; Cryoglobulinemic Glomerulonephritis
Cardiovascular disease (CVD) is the leading cause of death in renal allograft recipients with functioning graft. Our study aimed to determine the incidence and the risk factors of cardiovascular disease after renal transplantation in Korea. We retrospectively analyzed 430 adult recipients who underwent kidney transplantation between January 1997 and February 2007. CVD was defined as a composite outcome of ischemic heart disease, cerebrovascular accident and peripheral vascular disease. Mean age of recipients was 40.0±11.8 yr. Mean duration of follow-up was 72±39 months. The cumulative incidence of CVD after renal transplantation was 2.4% at 5 yr, 5.4% at 10 yr and 11.4% at 12 yr. Multivariate analysis revealed that recipient's age, diabetes mellitus and duration of dialysis before transplantation were associated with post-transplant CVD (hazard ratio 1.843 [95% CI, 1.005-3.381], 3.846 [95% CI, 1.025-14.432] and 3.394 [95% CI, 1.728-6.665] respectively). In conclusion, old age, duration of dialysis and diabetes mellitus are important risk factors for post-transplant CVD, although the incidence of post-renal transplant CVD is lower in Korea than that in western countries.
Cardiovascular Diseases; Incidence; Kidney Transplantation; Risk Factors; Diabetes Mellitus; Koreans
Marginal grafts should be used more actively in Asian countries where deceased donor transplantation is unpopular. We modified a quantitative donor scoring system proposed by Nyberg and his colleagues and developed a donor scoring system in order to assess the quality of deceased donor grafts and their prognostic value as an initial effort to promote usage of marginal donors.
Materials and Methods
We retrospectively evaluated 337 patients.
A scoring system was derived from six donor variables [age, 0-25; renal function, 0-4; history of hypertension, 0-4; Human Leukocyte Antigen (HLA) mismatch, 0-3; body weight, 0-1; cause of death, 0-3 points]. Donor grafts were stratified by scores: grade A, 0-10; grade B, 11-20; grade C, 21-30; and grade D, 31-40 points. Donor grades significantly correlated with estimated glomerular filtration rate (eGFR) at 6 months (A, 64.0 mL/min/1.73 m2; B, 57.0 mL/min/1.73 m2; C, 46.8 mL/min/1.73 m2; p < 0.001). The five-year graft survival rate was also lower in grade C than grade A (74% vs. 93%, p = 0.002). Donors in grade C and D were regarded as marginal donors. The proportion of marginal donors was much lower in Korea, compared with data from the United Network for Organ Sharing (15.2% vs. 29%).
Considering the scarcity of deceased donor kidneys and the relatively better graft outcome with lower grade-donors in Korea, it is worth increasing the usage of marginal grafts.
Kidney transplantation; cadaver; donor selection
We describe a case of infrarenal aortic hypoplasia in a 52-yr-old woman who presented with claudication. Computed tomographic angiography revealed an abrupt absence of the infrarenal aorta, with collateral flow reconstituting the iliofemoral systems. After a polytetrafluoroethylene graft was interposed between the aortic stump and the iliac bifurcation, the patient's claudication resolved.
Aortic Coarctation; Intermittent Claudication
Macrophage infiltration has been observed in the renal biopsy specimens of diabetic nephropathy (DN), and hyperglycemic state stimulates the renal expression of RANTES (regulated upon activation, normal T-cell expressed and secreted) and MCP-1 (monocyte chemoattractant protein-1). Upregulation of RANTES and MCP-1 with infiltrating macrophages may play a crucial role in the development and progression of DN. Genetic polymorphisms of RANTES and its receptors were reported to be independent risk factors for DN. We genotyped single nucleotide polymorphism (SNPs) in the MCP-1 G-2518A, CCR2 G46295A, RANTES C-28G and G-403A in 177 diabetic end-stage renal disease (ESRD) patients and 184 patients without renal involvement (controls) in order to investigate the effects of these SNPs on DN in Korean patients with type 2 DM. There were no differences in the frequencies of SNPs and the distribution of haplotypes of RANTES promoter SNPs between two groups. In conclusion, there were no associations of MCP-1, CCR2 and RANTES promoter SNPs with diabetic ESRD in Korean population. Prospective studies with clearly-defined, homogenous cohorts are needed to confirm the effect of these genetic polymorphisms on DN.
Diabetic Nephropathies; Kidney Failure, Chronic; Monocyte Chemoattractant Proteins; RANTES; Polymorphism, Single Nucleotide Polymorphisms; Diabetes Mellitus, Type 2