Abnormal serum potassium is associated with higher mortality in dialysis patients, but its impact on outcomes in predialysis chronic kidney disease (CKD) is less clear. Furthermore, blacks with normal kidney function have lower urinary potassium excretion, but it is unclear if such differences have a bearing on race-associated outcomes in CKD.
We studied predialysis mortality and slopes of estimated glomerular filtration rate, eGFR) associated with serum potassium in 1,227 males with CKD. Mortality was examined in time-dependent Cox models, and slopes of eGFR in linear mixed effects models with adjustments for case mix and laboratory values.
Both hypo- and hyperkalemia were associated with mortality overall and in 933 white patients, but in 294 blacks hypokalemia was a stronger death predictor. Hypokalemia was associated with loss of kidney function independent of race: a 1 mEq/l lower potassium was associated with an adjusted difference in slopes of eGFR of −0.13 ml/min/1.73 m2/year (95% CI: −0.20 to −0.07), p < 0.001.
Hypo- and hyperkalemia are associated with higher mortality in CKD patients. Blacks appear to better tolerate higher potassium than whites. Hypokalemia is associated with faster CKD progression independent of race. Hyperkalemia management may warrant race-specific consideration, and hypokalemia correction may slow CKD progression.
Serum potassium; Chronic kidney disease; Mortality; Race; Glomerular filtration rate
Background: Relapse or worsening of nephrotic syndrome (NS) in idiopathic membranous nephropathy (IMN) is generally assumed to be due to recurrent disease. Here we document that often that may not be the case. Subjects and Methods: This is a prospective study of 7 consecutive IMN patients whose renal status improved, then worsened after completing a course of immunosuppressive therapy. Each underwent detailed testing and repeat kidney biopsy. Results: In 4 patients (group A), the biopsy showed recurrent IMN (fresh subepithelial deposits). Immunosuppressive therapy was begun. In the other 3 patients (group B), the biopsy showed that the deposits had been eradicated. However, the glomerular basement membrane (GBM) was thickened and vacuolated. Immunosuppressive therapy was withheld. Groups A and B were comparable except that group B had very high intakes of salt and protein, based on 24-hour urine testing. Reducing their high salt intake sharply lowered proteinuria to the subnephrotic range and serum creatinine stabilized. Conclusion: This work is the first to demonstrate that relapse/worsening of NS can occur in IMN even though the GBM deposits have been eradicated. High salt and protein intake in combination with thickened and vacuolated GBM appears to be the mechanism.
Relapse of membranous nephropathy; Salt intake; Eradication of GBM deposits
There have been considerable advances in the past few years in our understanding of how chronic kidney disease (CKD) predisposes to acute kidney injury (AKI) and vice versa. This review shows, however, that few studies have focused on the elderly or conducted stratified analysis by age. It does appear that elderly patients with estimated glomerular filtration rate (eGFR) 45–59 ml/min/1.73 m2 are at higher risk for AKI compared with their counterparts with eGFR >60 ml/min/1.73 m2. This is a similar relationship to that seen in younger patients, although effect size appears smaller. As the incidence of AKI has been increasing over the past several years, the proportion of elderly patients surviving after AKI has also been increasing. Since AKI heightens the risk for the development and acceleration of CKD, this implies significant public health concerns with regard to the absolute number of elderly persons developing incident CKD.
Acute kidney injury; Aging; Chronic kidney disease; Glomerular filtration rate
Some day we will have powerful targeted therapies for autoimmune diseases. Remission will be induced efficiently. Side effects will be mere ripples. Unfortunately, that day is not imminent. Current therapies are powerful but with unintended targets and side effects that can be equivalent to a sea change. For SLE, the current competition to select the ‘gold standard’ immunosuppressant has come down to two regimens: intravenous cyclophosphamide (IVCY, standard NIH protocol or its variations) versus oral mycophenolate (MMF). Until recently, IVCY reigned as the gold standard, a title it achieved through a curious journey that did not involve rigorous head-to-head competition. Oral cyclophosphamide (POCY) has not been invited to the current competition to select the gold standard immunosuppressant despite the substantial evidence that POCY can perform at least as well as IVCY or mycophenolate, and compared to IVCY, is far less expensive, easier for the patient, and maybe more effective in African-Americans. Here, we state the case for POCY as therapy for severe autoimmune diseases. We suggest that if POCY is allowed to compete, it will not disappoint.
SLE nephritis; Oral cyclophosphamide; Intravenous cyclophosphamide
Identifying methods to accurately measure the glomerular filtration rate (GFR) in obese individuals without kidney overt kidney disease is necessary to understanding the pathophysiology and natural history of obesity-related kidney disease.
Using a cross-sectional design, iohexol clearance and disposition was measured, an optimal sampling schedule was identified, and the reliability of GFR-estimating methods was described in 29 obese individuals with normal serum creatinine levels. Iohexol disposition was measured using population pharmacokinetics. The agreement with GFR-estimating equations was assessed by intraclass coefficients.
Mean age was 44 ± 10 years, body mass index 45 ± 10, creatinine 0.7 ± 0.2 mg/dl (62 ± 18 μmol/l), and cystatin C 0.83 ± 0.18 mg/dl (8.3 ± 1.8 mg/l). Iohexol disposition fit a two-compartment model and 5 sampling windows were identified over a 4-hour period to optimize model accuracy and minimize blood draws. Precision was not compromised with this sampling design. Neither creatinine nor cystatin C were linearly correlated with the measured GFR though cystatin C was independent of body composition. Agreement was fair to poor between the measured GFR and GFR-estimating equations.
This study offers a rigorous method to study obesity-related kidney disease and improve upon suboptimal GFR-estimating methods.
Iohexol; Glomerular filtration rate; Creatinine; Cystatin C; Obesity
The high risk and prevalence of dementia among patients with chronic kidney disease (CKD) and in those receiving hemodialysis (HD) may be preceded by mild cognitive impairment (MCI). We aimed to assess cognitive function in CKD and HD patients with no history of stroke or dementia, in order to identify and characterize early cognitive deficits.
24 CKD and 27 HD male outpatients without history of cerebrovascular or neurodegenerative disease underwent comprehensive neuropsychological testing in an observational cross-sectional study. Test results were used to categorize patients into MCI subtypes.
All subjects scored ≥28 on the Mini-Mental State Examination. The prevalence of executive function was at least 25% in both groups and memory impairment occurred in 13% of the HD patients and 15% of those with CKD. MCI occurred in 76% of the group and HD patients showed a higher prevalence of MCI compared to CKD patients (89 vs. 63%) with a preponderance (>70%) of cases across both groups classified as non-amnestic MCI.
Predialysis CKD and HD patients have a high prevalence of MCI despite normal global cognitive function. MCI was more prevalent among the HD patients and deficits more frequently resulted in non-amnestic MCI.
Cognition; Mild cognitive impairment; Cerebrovascular disease; Chronic kidney disease; Hemodialysis
There is increasing interest in the delivery of out-of-center hemodialysis (HD), particularly in the home setting, but little systematic information about its use and outcome in contemporary incident patients is available.
Patients and Methods
Out-of-center HD was defined as HD delivered in a residential setting, mainly at home or in a long-term care facility (such as a nursing home) irrespective of the length and frequency of therapy. All-cause mortality was determined in an observational cohort study of 458,329 adult patients initiating dialysis in the United States with Medicare as a primary payer.
Between 1995 and 2004, out-of-center HD was the initial modality in 1,641 (0.4%) of eligible participants, although there was significant geographic variation. Patients initiating out-of-center HD were younger, more likely to be nonwhite, had fewer comorbidities, a higher median income, and were more likely to be employed than patients initiating in-center HD or peritoneal dialysis (PD). In multivariate analysis, out-of-center HD patients had a higher overall risk of death compared to in-center HD or PD patients (HR = 1.10, 95% CI 1.04, 1.17), although the relative risk of death was lower in younger and healthier patients (HR = 0.78; 95% CI 0.61, 1.00).
Out-of-center HD is not associated with a survival advantage among unselected patients initiating dialysis in the United States. These results call for better characterization of out-of-center HD in national registries, primarily to effectively compare the use, outcomes and potential benefits of home HD to standard therapies.
Home setting; Out-of-center hemodialysis; Hemodialysis; Peritoneal dialysis; Long-term care facility; Survival
Sorry, there is no abstract.
The prevalence and associated risk factors for albuminuria and low-grade albuminuria in Alaska Natives is not known.
Cross-sectional analysis of the Genetics of Coronary Artery Disease in Alaska Natives Study. We included 1,026 individuals, who represent 85% of the study participants for whom complete data were available. Risk factors examined were age, sex, education, diabetes, hypertension, obesity, lipids, C-reactive protein, angiotensin-converting enzyme inhibitor use, and smoking status. Urine albumin excretion was estimated by the albumin/creatinine ratio measured from a single random morning urine sample. Albuminuria was defined as an albumin/creatinine ratio of ≥30 mg/g. Low-grade albuminuria was defined as an albumin/creatinine ratio of 10 to <30 mg/g.
The mean age was 42 years and over half were female. Diabetes prevalence was low at 3% and the prevalence of hypertension was 20%. The prevalence of albuminuria was 6%; the prevalence of low-grade albuminuria was 12%. Individuals with diabetes or hypertension were 3 times more likely to have albuminuria than those without these conditions [odd ratios: diabetes 3.0 (1.2–7.9) and hypertension 3.0 (1.2–7.3)].
The burden of albuminuria is low. Comprehensive programs and policies are important given the rise in diabetes and hypertension among Alaska Natives.
Albuminuria; Kidney disease; Alaska Natives; Risk factor; Epidemiology
In cross-sectional analyses, C-reactive protein (CRP) levels are inversely related to levels of kidney function. The relationship between kidney function and subsequent changes in CRP is unknown.
We studied 4,364 individuals from the Cardiovascular Health Study, a longitudinal cohort of community-dwelling older adults. Baseline eGFRcys was estimated using cystatin C. CRP was measured at baseline and after 3 and 7 years of follow-up; slopes of change in CRP were calculated.
The mean (SD) age of the cohort was 72 (5.2) years; mean (SD) eGFRcys was 78.9 (18.4) ml/min/1.73 m2. The median (interquartile range IQR) baseline CRP was 2.39 (1.22, 4.33) mg/l; the median (IQR) yearly change in CRP was −0.0051 (−0.020 to 0.27) mg/l/year. After adjustment for demographic characteristics and the initial level of CRP, each standard deviation lower baseline eGFR was associated with a small and non-significant yearly increase in CRP (0.032 mg/l/year; 95% CI: −0.005 to 0.070, p = 0.094).
We did not find a relationship between eGFR and subsequent changes in CRP. The association between kidney function and CRP in cross-sectional analyses may reflect unmeasured confounding by atherosclerosis; alternatively, the burden of comorbidity and interval mortality in this population may have masked a stronger longitudinal association between kidney function and change in CRP. Further study in younger populations may clarify whether impaired kidney function leads to change in inflammation over time.
Inflammation; Cystatin C; Kidney function; Epidemiology
We had previously reported that acute kidney injury (AKI) in warfarin-treated chronic kidney disease (CKD) patients may occur shortly after an acute increase in the International Normalization Ratio (INR) >3.0 with formation of occlusive red blood casts. Recovery from this warfarin-associated AKI is poor. Here we investigated whether excessive warfarin therapy could accelerate the progression of CKD.
We analyzed serum creatinine (SC) and INR in 103 consecutive CKD patients on warfarin therapy in our Nephrology program from 2005 to the present.
Forty-nine patients experienced at least 1 episode of INR >3.0. Of these, 18 patients (37%, Group 1) developed an unexplained increase in SC ≥0.3 mg/dl coincident with INR >3.0 (mean SC increase 0.61 ± 0.44 mg/dl); 31 patients (63%, Group 2) showed stable SC (mean SC change 0.04 ± 0.19 mg/dl). Subsequent CKD progression was accelerated in Group 1, but not in Group 2. The 2 groups were not different with respect to demographics, comorbidities, blood pressure, or therapies. However, African Americans were overrepresented in Group 1 (p = 0.035).
Overanticoagulation is associated with faster progression of CKD in a high percentage of patients. Our results indicate the need for prospective trials. Nevertheless, we suggest that our findings are sufficiently compelling at this point to justi- fy extra caution in warfarin-treated CKD patients to avoid overanticoagulation.
Warfarin; Serum creatinine; Acute kidney injury; Chronic kidney disease
The catecholaminergic pathway is important in the physical stress response; however, its role is not well understood in acute kidney injury (AKI). We studied single nucleotide polymorphisms (SNPs) of phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the catecholaminergic pathway, and their association with adverse outcomes in AKI.
We performed a case-control study of 961 Caucasian subjects (194 with AKI and 767 controls). The PNMT promoter G–161A (rs876493) and coding A+1543G (rs5638) SNPs were genotyped and haplotypes generated. The outcomes of interest were the development of AKI, in-hospital mortality, dialysis requirement, oliguria, and hemodynamic shock. Urine catecholamines were measured in cases to explore genotype-phenotype correlations.
The PNMT +1543 G allele was associated with AKI [odds ratio (OR) 2.19, 95% confidence interval (CI): 1.04–4.60]. For AKI cases, each PNMT −161 A allele was associated with lower mortality (OR 0.58, 95% CI: 0.35–0.99) and hemodynamic shock (OR 0.63, 95% CI: 0.40–1.00). The PNMT +1543 G allele was associated with oliguria (OR 3.35, 95% CI: 1.13–9.95). Urine adrenaline was associated with increased hemodynamic shock and mortality, but was lowest in PNMT −161 A/A carriers.
In Caucasians, PNMT SNPs are associated with the development of AKI, disease severity, and in-hospital mortality. The adrenergic pathway provides another area of focus in the study of AKI.
Acute kidney injury; Phenylethanolamine N-methyltransferase; Single nucleotide polymorphisms; Mortality
Little is known about the association of chronic kidney disease (CKD) with sleep quality, mood, and alertness. In this report, we assessed these symptoms among patients with advanced CKD (stages 4–5) and those with end-stage renal disease (ESRD) and compared them to healthy controls without known kidney disease.
Patients were recruited from local dialysis units, outpatient nephrology clinics and the Thomas E. Starzl Transplant Institute. Healthy control subjects matched for age, gender and race were drawn from an archival database. Daily symptoms of sleep quality, mood, and alertness were assessed by visual analogue scales of the Pittsburgh Sleep Diary. Health-related quality of life was assessed by the Short Form-36 instrument.
Sixty-nine dialysis patients and 23patients with advanced CKD demonstrated worse scores in sleep quality, mood, and alertness (p < 0.001) than controls. In adjusted analyses, European-American race, dialysis dependency, younger age, and physical performance SF-36 components were significantly associated with poor sleep quality, mood and alertness (p < 0.05). The dialysis population demonstrated higher day-to-day variability in scores than either the advanced CKD patients or the controls.
Advanced CKD and dialysis dependency are associated with impaired and highly variable sleep quality, mood, and alertness.
Mood; Sleep quality; Alertness; Chronic kidney disease; End-stage renal disease; Pittsburgh Sleep Diary; SF-36
Inpatient initiation of chronic hemodialysis is considered undesirable because of cost and possible harms of hospitalization. We examined the patient characteristics and outcomes associated with inpatient initiation.
In a prospective cohort study of incident dialysis patients, the independent association of inpatient hemodialysis initiation with patient outcomes was assessed in multivariable analyses with adjustment for patient characteristics and propensity for inpatient initiation.
A total of 410 of 652 (63%) hemodialysis patients began as inpatients; uremia and volume overload were the most commonly documented reasons. Compared to outpatients, inpatients were more likely to be unmarried, report less social support, have multiple comorbidities and be referred to a nephrologist 4 months or less prior to initiation. Inpatient initiation was protective for subsequent all-cause hospitalization (incidence rate ratio (IRR) = 0.92, confidence interval (CI) 0.89–0.94); this was most pronounced among those who had the highest propensity for inpatient initiation (IRR = 0.66, CI 0.56–0.78), including those referred late to nephrology. Similar results were found for infectious hospitalization. Mortality [hazard ratio = 1.03, CI 0.82–1.30] and cardiovascular events were not significantly different for inpatients versus outpatients.
Inpatient hemodialysis initiation has a protective association with hospitalization among those patients referred late to nephrology, with multiple comorbidities and/or little social support.
End-stage renal disease; Hospitalization; Late referral; Mortality; Social support
Cardiopulmonary bypass (CPB) elicits an inflammatory response mediated partly by neutrophils, which are activated and recruited by interleukin-8 (IL-8). We hypothesized that acute kidney injury (AKI) following CPB might be mediated by IL-8 and examined the association of perioperative plasma IL-8 levels with AKI in a prospective cohort.
Plasma IL-8 was measured before, and 2, 24 and 48 h following CPB. Two AKI definitions, a serum creatinine increase of ≥0.3 mg/dl or 50% (AKI Network [AKIN] stage-1) or ≥50% alone (AKI-50%), within the first 72 h, were used. Area under the receiver operator characteristic curves (AUCs) were generated and multivariable logistic regression analyses performed.
A total of 143 patients were enrolled. The baseline mean serum creatinine was 1.1 mg/ dl (SD = 0.3), the CPB perfusion time was 112 min (SD = 43). Twenty-nine percent of the patients developed AKIN stage-1 and 13% AKI-50%. The plasma IL-8 level 2 h after CPB was higher in AKIN stage-1 (p = 0.03) and AKI-50% (p < 0.01), and predicted AKIN stage-1 (AUC = 0.62; p = 0.02) and AKI-50% (AUC = 0.72; p < 0.01). On multivariable analysis, the 2-hour plasma IL-8 level was associated with 1.36- and 1.59-fold higher odds for AKIN stage-1 and AKI-50%, respectively (p = 0.05).
Plasma IL-8 predicts the development of AKI following CPB, supporting a potential involvement for this chemokine in the pathogenesis of AKI.
Cardiac surgery; Acute kidney injury; Chemokine; Interleukin-8
Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic lupus erythematosus (SLE) glomerulonephritis (GN). Shortly afterward, 2 works were published, designated Study 1 and Study 2, which are the only studies to test spot P/C in SLE GN. Here we evaluate Study 1 and Study 2, which came to different conclusions.
Study 1 compared spot P/C to the P/C of intended 24-hour collections >50% complete, which reliably estimates 24-hour proteinuria. Study 2 compared spot P/C to the protein content of intended 24-hour collections >80% complete. To compare studies, Study 2 data were converted to P/C ratios.
Study 1 and Study 2 were found to be in agreement. Both showed that spot P/C and 24-hour P/C were highly correlated, but only when compared over the entire P/C range (0–8.0) (r = 0.842). Over the P/C range 0.5–3.0 (the most common P/C range encountered in SLE GN), correlation was present, but concordance was poor, rendering random P/C ratio unreliable.
Random spot P/C ratio is unreliable for detecting moderate proteinuria change. For example, random spot P/C would not reliably diagnose British Isles Lupus Assessment Group (BILAG) Category A or B proteinuric flares.
SLE glomerulonephritis; Proteinuria; SLE flare
Anemia in chronic kidney disease is an independent predictor of cardiovascular disease (CVD). We explored the relationship between anemia and markers of inflammation and endothelial activation in non-dialysis chronic kidney disease (ND-CKD) patients to understand this mechanism.
Cross-sectional analysis was performed on 30 adult ND-CKD patients for markers of inflammation and endothelial activation using a multiplexed immunoassay. Data were analyzed according to the anemic status defined by the modified World Health Organization criteria.
Seventeen patients were classified as anemic. Baseline characteristics by anemic status were similar except that anemic patients were older (p = 0.006), had lower estimated glomerular filtration rate (eGFR; p = 0.01) and higher prevalence of CVD (p = 0.02). Compared to non-anemic patients, log-transformed values of fibrinogen (p = 0.012); von Willebrand factor (vWF, p = 0.008), vascular cell adhesion molecule-1 (VCAM-1, p = 0.025) and C-reactive protein (p = 0.043) were elevated in anemic patients. Serum ferritin (p = 0.93) and serum albumin (p = 0.06) were not different. Age and eGFR-adjusted logistic regression analysis showed that anemic patients had increased odds for a composite of higher median values of fibrinogen, vWF and VCAM-1 (p = 0.01, odds ratio 8.1, 95% CI 1.08–111.0).
We report the association of anemia with elevated markers of endothelial activation in ND-CKD patients. Longitudinal studies are needed to confirm our findings.
Anemia; Chronic kidney disease; Endothelial markers; Fibrinogen; Vascular cell adhesion molecule-1; Von Willebrand factor
Lanthanum carbonate (LC, FOSRENOL®) is an effective phosphate binder for which tolerability and a safety profile have been reported in haemodialysis patients. Patients from previous studies entered a 2-year extension, enabling assessment of efficacy and safety for up to 6 years of LC monotherapy.
Patients from four previous trials entered this study.
Ninety-three patients started the extension, with 22 entering a sixth year of LC treatment. Two-thirds of all patients received LC doses of 2,250 or 3,000 mg/day. Reductions in serum phosphate and calcium × phosphate product were maintained for up to 6 years. There were no new or unexpected adverse events (AEs), and no increase in the incidence of events with increasing treatment exposure. Over the complete duration of therapy, treatment-related AEs occurred in 25.8% of patients and were primarily gastrointestinal in nature. No clinically relevant changes in liver function tests were observed and there was no evidence of adverse effects on the liver, bone or the central nervous system.
LC monotherapy was effective and well tolerated for up to 6 years with no evidence of safety concerns or increased frequency of AEs.
Lanthanum carbonate; Hyperphosphatemia; Clinical trial