Design, setting, participants, & measurements: A total of 111 CKD patients (79 men, 32 women; glomerular filtration rate [GFR] median, 33.7 ml/min per 1.73 m²), free of cardiovascular disease, were consecutively recruited along with 30 age-matched healthy subjects. Coronary artery calcification scores (CACS) were measured by multidetector-row CT according to Agatston score.

Results: In CKD patients, CACS was distributed widely from 0 to 2901, while in age-matched, healthy control subjects (n = 30), CACS showed a range from 0 to 307. GFR had a significant negative correlation with CACS. Plasma ADMA levels were negatively correlated with GFR and positively correlated with CACS. When CACS was divided into quartiles (<50, n = 56; 50 to 300, n = 24; 300 to 600, n = 14; >600, n = 17), the patients with CACS >600 had significantly higher values of HOMA-IR, plasma ADMA levels, and fibrinogen along with serum levels of phosphorus, compared with those in patients having CACS <50. Multivariate regression analysis determined HOMA-IR as an independent contributing factor to CACS.

Conclusions: CAC becomes more prevalent and severe with a decline in GFR, and plasma ADMA levels and insulin resistance, independent of factors associated with CKD-MBD, are correlated with CAC.

Design, setting, participants, and measurements: Cross-sectional data from 3089 adult outpatients, who were consecutively referred by general practitioners for routine blood testing over the last two years, were analyzed. Glomerular filtration rate (GFR) was estimated by the abbreviated Modification of Diet in Renal Disease equation. Multivariable logistic regression was used to evaluate the independent association between prevalent subclinical primary hypothyroidism and estimated GFR.

Results: Among 3089 adult participants, 293 (9.5%) had subclinical primary hypothyroidism and 277 (9%) had an estimated GFR <60 ml/min per 1.73 m². The prevalence of subclinical primary hypothyroidism increased from 7% at an estimated GFR ≥90 ml/min per 1.73 m² to 17.9% at an estimated GFR <60 ml/min per 1.73 m² (P < 0.0001 for trend). Compared with participants with an estimated GFR ≥60 ml/min per 1.73 m², those with estimated GFR <60 ml/min per 1.73 m² had an increased odds of subclinical primary hypothyroidism after adjusting for age, gender, fasting plasma glucose, total cholesterol, and triglyceride concentrations.

Conclusions: These findings suggest that subclinical primary hypothyroidism is a relatively common condition (~18%) among persons with CKD not requiring chronic dialysis, and it is independently associated with progressively lower estimated GFR in a large cohort of unselected outpatient adults.

Design, setting, participants, & measurements: Fifty-five patients were followed up for 54.0 ± 21.2 mo. Thirty-five of them underwent tonsillectomy and steroid pulse therapy (group C), and 20 received steroid pulse monotherapy (group M). Both groups received methylprednisolone intravenously, followed by oral prednisolone (initial dosage 0.5 mg/kg per d) for 12 to 18 mo. Primary evaluation items were a 100% increase in serum creatinine from baseline levels or the disappearance of urinary protein (UP) and/or occult blood (UOB) indicating clinical remission.

Results: At 24 mo after the initial treatment, the ratios of the UP and UOB disappearance were higher in group C than in group M, and the therapeutic effect persisted until the final observation. None of group C achieved a 100% increase in serum creatinine from the baseline level, whereas one patient in group M developed ESRD during the observation period. The histologic findings of repeated biopsy specimens from 18 patients revealed that mesangial proliferation and IgA deposition were significantly more reduced in group C than in group M. The Cox regression model showed that the combined therapy was approximately six-fold more effective in causing the disappearance of UP than steroid pulse monotherapy.

Conclusion: Tonsillectomy combined with steroid pulse treatment can induce clinical remission in patients with IgA nephropathy.

Design, setting, participants, & measurements: SES was assigned to each patient according to electoral ward of residence by postcode and ranked according to the corresponding British Index of Multiple Deprivation score, which comprises five deprivation quintiles (Q1, least deprived; Q5, most deprived). National Kidney Foundation Kidney Disease Outcomes Quality Initiative classification of CKD was used for stratification and analysis. Binary logistic regression analysis was applied for the association of variables/risk factors with CKD (lower GFR) at presentation.

Results: The age-adjusted prevalence of diagnosed CKD at presentation by area of residence, across the five deprivation quintiles, per million population was Q1 = 1495, Q2 = 3530, Q3 = 3398, Q4 = 3989, and Q5 = 19,599. Logistic regression models showed that living in the lowest SES quintile area (Q5) as compared with the highest SES (Q1) was associated with a greater risk for presenting with a lower estimated GFR, after adjustment for sociodemographic, lifestyle, and clinical variables.

Conclusions: Low SES is related to severity of CKD at presentation. Further studies are needed to examine this issue across the various SES categories in the United Kingdom.

Design, setting, participants, & measurements: The impact of psychotropic medications on urinary concentrating ability and urinary aquaporin 2 (AQP2) excretion was investigated after overnight fluid deprivation, and over 6 h after 40 µg of desmopressin (dDAVP), in patients on lithium (n = 45), compared with those on alternate psychotropic medications (n = 42).

Results: Those not on lithium demonstrated normal urinary concentrating ability (958 ± 51 mOsm/kg) and increased urinary excretion of AQP2 (98 ± 21 fmol/µmol creatinine) and cAMP (410 ± 15 pmol/µmol creatinine). Participants taking lithium were divided into tertiles according to urinary concentrating ability: normal, >750 mOsm/kg; partial nephrogenic diabetes insipidus (NDI), 750 to 300 mOsm/kg; full NDI, <300 mOsm/kg. Urinary AQP2 concentrations were 70.9 ± 13.6 fmol/µmol creatinine (normal), 76.5 ± 10.4 fmol/µmol creatinine (partial NDI), and 27.3 fmol/µmol creatinine (full NDI). Impaired urinary concentrating ability and reduced urinary AQP2, cAMP excretion correlated with duration of lithium therapy. Other psychotropic agents did not impair urinary concentrating ability. Eleven patients on lithium were enrolled in a randomized placebo-controlled crossover trial investigating the actions of amiloride (10 mg daily for 6 wk) on dDAVP-stimulated urinary concentrating ability and AQP2 excretion. Amiloride increased maximal urinary osmolality and AQP2 excretion.

Conclusions: By inference, amiloride-induced reduction of lithium uptake in the principal cells of the collecting duct improves responsiveness to AVP-stimulated translocation of AQP2 to the apical membrane of the principal cells.

Design, setting, participants, & measurements: A retrospective cohort study of subjects who had been enrolled in the MDRD Study A and who had two or more contemporaneous assessments of mGFR and eGFR (n = 542; mGFR range, 25 to 55 ml/min per 1.73 m²) during the chronic phase (month 4 and afterwards). mGFR was based on urinary iothalamate clearance; eGFR was based on the 4-variable MDRD Study equation. Temporal changes in GFR were assessed by within-subject linear regression of time on GFR.

Results: Median follow-up time for all subjects was 2.6 yr; median number of GFR measurements was six. The eGFR slope tended to underestimate measured decrements in GFR. The absolute value of the difference in mGFR and eGFR slopes was ≤2 ml/min per 1.73 m² per yr among 58.3% of subjects; the remainder of subjects had larger absolute differences. Among the 22 variables studied, none predicted a systematic difference between mGFR slope and eGFR slope.

Conclusions: Although eGFR and mGFR exhibited similar relationships to 22 baseline variables, the overall bias seen in the full cohort suggests that clinicians and researchers should exercise caution when interpreting eGFR slope as a marker of progression of kidney disease.

Design, setting, participants, & measurements: Fourteen patients with a circulating monoclonal IgM and a kidney disease related to B cell proliferation were identified retrospectively. Demographic, clinical, and laboratory data were assessed for each patient at the time of kidney biopsy.

Results: Seven patients had a nephrotic syndrome. Patients without nephrotic syndrome all had impaired renal function. Mean serum creatinine was 238 µmol/L. For five patients, the diagnosis of monoclonal IgM preceded the kidney disease by 28.8 mo (range 12 to 60). Seven patients had Waldenström disease, two had a small B cell non-Hodgkin lymphoma, one had an IgM-excreting multiple myeloma, one had a marginal zone B cell lymphoma, and three had an IgM-related disorder. Renal lesions included (1) intracapillary monoclonal deposits disease with granular, electron-dense IgM thrombi occluding capillary lumens (5); (2) atypical membranoproliferative glomerulonephritis (3); (3) light chain amyloidosis (2) associated with µ deposits in one patient; (4) acute tubular necrosis (1); and (5) CD20⁺ lymphomatous infiltration (3). Remission of the nephrotic syndrome was attained in three of seven patients, and renal function improved after chemotherapy.

Conclusions: Although renal complications of IgM proliferations are rare, a wide spectrum of kidney lesions is observed, without correlation with the type of hematologic disorder.

Design, setting, participants, & measurements: A retrospective review was conducted of medical records, clinical presentations, laboratory findings, and underlying diseases for all cases of dengue infection in a medical center. Characteristics and outcomes of dengue-infected patients with and without RF were compared.

Results: From January 2002 through January 2003, 519 dengue-infected patients were enrolled, including 412 patients with classical dengue fever (DF) and 107 patients with dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Twelve patients died in this outbreak, and all had DHF/DSS. Twenty-one (4.0%) patients were defined as being in the RF group. The RF group had a higher mortality rate than non-RF group (28.6 versus 1.2%; P < 0.001). The severity of GFR impairment was associated with higher percentages of DHF/DSS (P = 0.029) and mortality (P < 0.001). Differences in symptoms/signs and laboratory abnormalities between DF and DHF/DSS were significant in the non-RF group but not apparent in the RF group.

Conclusions: The diagnosis and management of dengue infection among patients with RF must be cautious, because complicated clinical courses with a higher mortality rate were well observed.

Design, setting, participants, & measurements: In 207 Swedish patients with stage 5 chronic kidney disease and 79 Turkish patients with type 2 diabetes and proteinuria and normal renal function, whether serum pentraxin 3 levels are associated with albuminuria and endothelial dysfunction was studied.

Results: Patients with stage 5 chronic kidney disease and a high degree of albuminuria more often had diabetes and higher levels of pentraxin 3, vascular cellular adhesion molecule-1, and blood pressure. Moreover, pentraxin 3 was independently associated with 24-h urinary albumin excretion. In patients with type 2 diabetes, pentraxin 3 was significantly higher than in control subjects. Patients with type 2 diabetes and more proteinuria had higher pentraxin 3, C-reactive protein, glycosylated hemoglobin, insulin, and homeostasis model assessment index as well as lower flow-mediated dilation and serum albumin. Pentraxin 3 was positively correlated with C-reactive protein, homeostasis model assessment index, and carotid intima-media thickness and negatively with flow-mediated dilation. Pentraxin 3 and glomerular filtration rate were independently associated with 24-h urinary protein excretion. Only pentraxin 3 and proteinuria were significantly and independently associated with flow-mediated dilation.

Conclusions: In two different renal cohorts, one of stage 5 chronic kidney disease and one of type 2 diabetes and normal renal function, pentraxin 3 was independently associated with proteinuria. Moreover, both pentraxin 3 and proteinuria were associated with endothelial dysfunction in patients with type 2 diabetes.

Design, setting, participants, & measurements: Thirty normotensive patients with autosomal dominant polycystic kidney disease (10 male, 20 female) with well-preserved renal function and 30 healthy subjects (12 male, 18 female) were included in the study. Coronary flow velocity reserve was measured at baseline and after dipyridamole infusion by echocardiography. Coronary flow velocity reserve was calculated as the ratio of hyperemic to baseline diastolic peak velocities.

Results: Carotid intima-media thickness was significantly higher in patients than in control subjects (0.80 ± 0.29 versus 0.54 ± 0.14 mm, respectively; P < 0.001). Moreover, coronary flow velocity reserve was significantly lower in patients than in control subjects (1.84 ± 0.39 versus 2.65 ± 0.68, respectively; P < 0.001).

Conclusions: Normotensive patients with autosomal dominant polycystic kidney disease with well-preserved renal function have significantly increased carotid intima-media thickness and significantly decreased coronary flow velocity reserve compared with healthy subjects. These findings suggest that atherosclerosis starts at an early stage in the course of their disease in patients with autosomal dominant polycystic kidney disease.

Design, setting, participants, & measurements: In a diverse population of hemodialysis patients, we compared mean serum creatinine concentrations in black versus nonblack patients, adjusting for case mix (age, gender, diabetes, and dialysis vintage), body size (height, weight), laboratory parameters of nutritional status (albumin, predialysis blood urea nitrogen, transferrin, phosphorus, glucose), dialysis dosage (urea reduction ratio), and parameters of bioelectrical impedance (resistance and reactance), proxies for body composition.

Results: Adjusted mean serum creatinine concentrations were significantly higher in black versus nonblack patients (11.7 versus 10.0 mg/dl; P < 0.0001). Black patients were roughly four-fold more likely to have a serum creatinine concentration >10 mg/dl and six-fold more likely to have a serum creatinine concentration >15 mg/dl. Higher serum creatinine concentrations were associated with a lower relative risk for death (0.93; 95% confidence interval 0.88 to 0.98 per mg/dl); the association was slightly more pronounced among nonblack patients.

Conclusions: Serum creatinine concentrations are significantly higher in black compared with nonblack hemodialysis patients; these differences are not readily explained by differences in nutritional status or body composition.

Design, setting, participants, & measurements: Albumin excretion rate was measured in 368 normal and 175 diabetic adolescents. Multiple regression analysis was used to predict the relation of age, sex, Tanner stage, body mass index, and systolic blood pressure to albumin excretion in both cohorts. In addition, correlations between albumin excretion and age, blood pressure, body mass index, lipids, and measurements of insulin resistance were performed in the normal adolescents.

Results: Mean albumin excretion was significantly lower in normal adolescents (4.0 µg/min) than in type 1 diabetic adolescents (5.0 µg/min). Albumin excretion increased with age in diabetics. Albumin excretion did not significantly correlate with any measure of cardiovascular risk or insulin resistance but did significantly correlate with fasting insulin.

Conclusions: Albumin excretion rate is not related to insulin resistance or traditional cardiovascular risk factors in adolescence but is related to fasting insulin. Diabetic adolescents have increased albumin excretion compared with normal adolescents.

Design, setting, participants, & measurements: Thirty-eight patients, enrolled from nine centers in the United States, were ≥18 yr of age and had hemoglobin <11.0 g/dl and GFR 12 to 60 ml/min per 1.73 m². Patients received one of four epoetin alfa dosing regimens: 50 IU/kg three times per week, 10,000 IU once weekly, or 20,000 IU every 2 wk for 36 d or 40,000 IU every 4 wk for 64 d. Each regimen provided a similar dosage of epoetin alfa over 4 wk. Dosage adjustments were not permitted.

Results: Drug exposure to epoetin alfa over 4 wk, based on area under the curve, was somewhat higher with the extended interval regimens compared with the three-times-weekly regimen. Mean change in hemoglobin during the study period was similar for all regimens. No patients were transfused. Three patients experienced five serious adverse events, none of which was considered treatment related.

Conclusions: Extended dosing interval regimens of epoetin alfa yielded modest pharmacokinetic differences but a similar pharmacodynamic response, suggesting that less frequent, higher dosages of epoetin alfa may be as effective as the current three-times-weekly regimen in anemic patients who have chronic kidney disease and are not on dialysis.

Design, setting, participants, & measurements: This open-label study randomized subjects (1:2:2:2) to treatment with epoetin alfa 10,000 IU QW, 20,000 IU Q2W, 20,000 IU Q4W, or 40,000 IU Q4W for 16 wk. Subjects were ≥18 yr, had hemoglobin <11 g/dl, a glomerular filtration rate of 15 to 90 ml/min per 1.73 m², and had not received erythropoietic therapy within 8 wk. The primary analysis was a noninferiority comparison of the 40,000 IU Q4W to the 20,000 IU Q2W group in the per-protocol population with respect to hemoglobin change from baseline to the end of study.

Results: Of 262 subjects randomized, 229 comprised the per-protocol population. Mean hemoglobin change from baseline for the 40,000 IU Q4W group (1.24 g/dl) was not inferior to the 20,000 IU Q2W group (1.11 g/dl) with the lower limit of 95% CI, –0.21 g/dl. In the QW, 20,000 IU Q2W, 20,000 IU Q4W, and 40,000 IU Q4W groups, 90%, 87%, 75%, and 86% of subjects, respectively, achieved a hemoglobin increase ≥1 g/dl. Serious adverse events were similar across all groups.

Conclusions: Epoetin alfa can be initiated Q4W in anemic CKD subjects.

Design, setting, participants, & measurements: For analysis of pathogenic mechanisms, a group of individuals were prospectively evaluated before and after candombe drumming.

Methods: Candombe drummers were recruited in January 2006, 1 wk before prolonged drumming. After clinical evaluation, urine and blood samples were obtained before and immediately after drumming.

Results: Forty-five healthy individuals (four women and 41 men), median age 31 yr (14 to 56), were evaluated. Predrumming urine and plasma samples were obtained for 30 individuals. Nineteen (42%) of 45 had a previous history of rust urine emission temporally related with candombe drumming. After drumming, 18 of 26 showed urine abnormalities; six of 26 showed rust urine, eight of 26 had microhematuria, and seven of 26 had proteinuria >1 g/L. The candombe drummers who showed rust urine after heavy drumming presented significantly higher levels of lactate dehydrogenase and total bilirubin when compared with those without urine abnormalities. Haptoglobin was significantly lower in the rust urine group. Fragmented red cells were observed in the blood smear of individuals with rust urine. Rust urine after drumming was associated with previous episodes of rust urine and glucosuria.

Conclusions: Taken together, these data confirm that rust urine is caused by extracorpuscular hemolysis.

Design, setting, participants, & measurements: Twenty-four-hour urine collections (n = 127) were obtained at baseline and annually for measurement of microalbumin, total protein, and creatinine.

Results: There was a strong linear relationship between microalbumin-creatinine and protein-creatinine ratios over the entire range of protein-creatinine ratios; however, in the protein-creatinine ratio range 0.0 to 0.3, as the protein-creatinine ratio increased, the microalbumin-protein ratio increased much more than the protein-creatinine ratio. Also, the greater the protein-creatinine ratio, the greater was the evidence for nonselective proteinuria (protein-creatinine ratio – microalbumin-creatinine ratio).

Conclusions: For the diagnosis of proteinuria renal flare, measuring albuminuria offers no advantage over measuring total proteinuria because changes in protein-creatinine and microalbumin-creatinine ratios are highly correlated over the designated ranges for systemic lupus erythematosus glomerulonephritis proteinuric flares. In those with normal-range proteinuria, subsequent changes in microalbumin-protein ratio might be a better forecaster of renal flare than changes in protein-creatinine or microalbumin-creatinine ratio. High protein-creatinine ratios are associated with evidence of nonselective proteinuria, which may increase the nephrotoxicity of proteinuria. Thus, using high-threshold criteria for systemic lupus erythematosus flare (allowing greater proteinuria increase before flare is declared) may expose the kidney to greater nephrotoxicity than using the low-threshold criteria for systemic lupus erythematosus flare.

Design, setting, participants, & measurements: A cross-sectional study was conducted of ambulatory patients without diabetes and with different stages of chronic kidney disease (n = 51), compared with gender- and age-matched healthy subjects. Fasting blood was obtained for measurement of advanced glycation end products and mRNA receptor for advanced glycation end product expression in peripheral blood mononuclear cells. Endothelial reactivity was assessed by the microcirculatory response to local ischemia (postocclusive reactive hyperemia) and local hyperthermia (thermal hyperemia). Sera were pooled and passed through affinity columns to separate advanced glycation end product–rich fractions, which were incubated with human aortic endothelial cells, with or without blockade of receptor for advanced glycation end product, to measure their effect on endothelial nitric oxide synthase.

Results: Glomerular filtration rate correlated with serum advanced glycation end product, mRNA receptor for advanced glycation end product levels, postocclusive reactive hyperemia, and thermal hyperemia. Serum advanced glycation end product correlated with receptor for advanced glycation end product and inversely with postocclusive reactive hyperemia. Advanced glycation end product–rich fractions from chronic kidney disease sera suppressed endothelial nitric oxide synthase expression of human aortic endothelial cells compared with sera from healthy subjects, an effect abrogated by receptor for advanced glycation end product blockade.

Conclusions: This study demonstrates for the first time an association of excess advanced glycation end product burden with increased peripheral blood mononuclear cell mRNA receptor for advanced glycation end product and in vivo endothelial dysfunction in patients with chronic kidney disease. Endothelial dysfunction in chronic kidney disease may be partly mediated by advanced glycation end product–induced inhibition of endothelial nitric oxide synthase through receptor for advanced glycation end product activation.

Design, Setting, Participants, and Measurements: We compared the effects of stent versus angioplasty on primary patency rates in the treatment of stenotic arteriovenous fistulae (AVF) and arteriovenous grafts (AVGs). Moreover, we compared access flow (Qa) and urea reduction ratio (URR) between the two groups as a metric of the effect of stent placement versus angioplasty on dialysis delivery.

Results: Cox regression analysis revealed that the primary assisted AVG patency was significantly longer for the stent group compared with angioplasty, with a median survival of 138 versus 61 d, respectively (aHR = 0.17; 95% confidence interval, 0.07 to 0.39; P < 0.001). The primary AVG patency for stent versus angioplasty was 91% versus 80% at 30 d, 69% versus 24% at 90 d, and 25% versus 3% at 180 d, respectively. The primary assisted AVF patency did not differ significantly between the stent and angioplasty groups. In patients dialyzing via AVF, multiple regression analysis revealed that stent placement was associated with improved after intervention peak Qa, 1627.50 ml/min versus 911.00 ml/min (β = 0.494; P = 0.008), change in Qa from before to after intervention, 643.54 ml/min versus 195.35 ml/min (β = 0.464; P = 0.012), and change in URR from before to after intervention, 5.85% versus 0.733% (β = 0.389; P = 0.039).

Conclusions: Our results suggest that stent placement is associated with improved AVG primary assisted patency and improved AVF blood flow, which may significantly impact on dialysis adequacy.