Identifying CKD in populations - SCORED

Nine-Question Survey Identifies Patients at Risk of Having Chronic Kidney Disease

Source - Medscape

The Screening for Occult Renal Disease (SCORED) questionnaire, which contains questions about demographic variables and health conditions, but does not require any laboratory test values, might be useful to identify individuals who are highly likely to have underlying chronic kidney disease (CKD).

Study Highlights

• This cross-sectional analysis included 8530 men and women 20 years or older in the NHANES, a nationally representative, US-population-based survey conducted from 1999-2000 and 2001-2002.
• Based on the literature, potential determinants of CKD evaluated for incorporation into SCORED were age, sex, race, marital status, anemia, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, hypertension, diabetes mellitus, peripheral vascular disease, history of cardiovascular disease, history of congestive heart failure, proteinuria, smoking status, physical activity, body mass index, educational and income levels, and health insurance status.
• The SCORED prediction model used univariate and multivariate associations between this comprehensive set of risk factors and CKD, defined as a glomerular filtration rate less than 60 mL/minute per 1.73 m². Optimal characteristics of the model were examined with internal measures, and a model-based numeric scoring system was developed. The Atherosclerosis Risk in Communities study was used for external validation.
• Combining NHANES 1999-2000 and 2001-2002 resulted in a data set of 10,291 individuals 20 years or older. Data from 8530 individuals were analyzed after exclusion of 1472 individuals with missing serum creatinine measurements and 289 with other missing covariates.
• 601 (5.4%) of 8530 participants had CKD. Their mean age was 46 years, and 52% were women; 72%, white; 10%, black; and 14%, Hispanic.
• Only 9 variables had statistically significant associations with CKD. These were age (P < .001), female sex (P = .02), hypertension (P = .03), diabetes (P = .03), peripheral vascular disease (P = .008), history of cardiovascular disease (P = .001), history of congestive heart failure (P = .04), proteinuria (P < .001), and anemia (P = .003). Age 50 to 59 years was assigned 2 points, 60 to 69 years was assigned 3 points, and 70 years and older was assigned 4 points. All other predictive features were assigned 1 point.
• The multivariate model was well validated in the internal and external data sets, with area under the receiver operating characteristic curve of 0.88 and 0.71, respectively.
• Based on both diagnostic and qualitative criteria and practical implementation considerations, a SCORED value of 4 or higher was chosen as a cutoff point for screening. This cutoff value yielded a sensitivity of 92%, specificity of 68%, positive predictive value of 18%, and negative predictive value of 99%.
• Study limitations include a model heavily weighted toward common risk factors for kidney disease, inability to determine family history of kidney disease, cross-sectional design, inability to rule out the possibility of developing CKD in the future, possible underestimation of CKD, and use of a statistical method unable to investigate complicated effect modifications among the risk and protective factors.

Diabetes Risk Score - German Study

German Diabetes Risk Score May Predict Development of Type 2 Diabetes

The German Diabetes Risk Score, which is based on anthropometric, dietary, and lifestyle factors, was an effective tool to identify patients at high risk or with undiagnosed diabetes, according to the results of a study reported in the March issue of Diabetes Care.

"The German Diabetes Risk Score (available at http://www.dife.de) is an accurate tool to identify individuals at high risk for or with undiagnosed type 2 diabetes," the authors write.

The European Union, the German Cancer Aid, the Federal Ministry of Science in Germany, the German Cancer Research Centre, the DFG, the German Ministry of Education and Science, and the Nationales Aktionsforum Diabetes Mellitus supported this study.

Diabetes Care. 2007;30:510-515.

Study Highlights

• The researchers applied their diabetes risk formula to several existing German study cohorts being followed up for incident diabetes. Study subjects were generally middle-aged adults, and diabetes was defined by a clinical diagnosis among most study subjects. A subset of participants underwent glucose tolerance testing.
• All subjects underwent an assessment of their health history and health habits, anthropometric data, diet, and exercise.
• The current diabetes risk scoring system was developed using one study cohort of 25,167 participants and was validated using another cohort of 23,398 subjects.
• The diabetes risk score was calculated using a formula involving waist circumference, height, age, the presence of hypertension, consumption of red meat, consumption of whole-grain bread, consumption of coffee, moderate alcohol use, physical activity, and a history of smoking.
• A score of 300 was associated with an incidence of diabetes of 0.3%, whereas a score of 750 portended a risk for diabetes of 23.2%.
• A score of 500 or more carried a sensitivity and specificity for predicting diabetes of 83.1% and 68.3%, respectively.
• Waist circumference was significantly and positively correlated with the risk for incident diabetes, even among younger participants.
• The German Diabetes Risk Score was also useful in diagnosing participants whose diabetes was diagnosed during glucose tolerance testing. A score of 500 or more carried a sensitivity between 82% and 93% and a specificity between 42% and 72% among this cohort.
• Overall, the German Diabetes Risk Score performed as well or better than previously used clinical risk assessments for type 2 diabetes.

Vit C Deficiency in MHD

NDT Advance Access originally published online on November 14, 2006
Nephrology Dialysis Transplantation 2007 22(2):328-331; doi:10.1093/ndt/gfl534

Vitamin C deficiency in dialysis patients—are we perceiving the tip of an iceberg?

Garry J. Handelman

University of Massachusetts, Lowell, MA 01854 and Renal Research Institute, New York, NY 10128, USA

Correspondence and offprint requests to: Garry J. Handelman, 3 Solomont Way, University of Massachusetts, Lowell, MA, 01854, USA. Email: garry_handelman@uml.edu

The occurrence of vitamin C deficiency has complicated the management of dialysis patients since the beginning of renal replacement therapy .
The major portion of dietary vitamin C is provided by potassium-rich foods such as orange juice, strawberries and broccoli, but these foods are restricted for haemodialysis (HD) patients .

Under these circumstances, low dietary vitamin C intake can readily occur.

Since vitamin C is partly metabolized to oxalate, which can accumulate in renal failure patients, many clinicians only recommend a dose of 60–100 mg/day, which may not be optimal.
The problem is made more severe by vitamin C losses during dialysis, which may remove several hundred mg of vitamin C in a single dialysis treatment .

Plasma vitamin C in dialysis patients is frequently <10> population. Normal plasma vitamin C levels in the non-dialysis population are 30–60 µM

Very high levels of vitamin C can also occur in dialysis patients, the effect of dialysis on vitamin C is highly variable. For patients who take large vitamin C supplements, the lack of the normal renal clearance mechanism can result in very high plasma levels (>200 µM)

Vitamin C deficiency can interfere with iron absorption and utilization, as well as leading to various abnormalities that are part of the syndrome of scurvy.

There is a situation where a large portion (10–25%) of dialysis patients have plasma vitamin C levels <10> plasma vitamin C <2> Epidemiological data suggest that these low plasma vitamin C levels are associated with increased mortality .

Although a 60–100 mg daily vitamin C supplement is generally recommended, prescriptions are provided only to 10–70% of patients, depending on nationality . Lack of compliance may lead to even lower levels of actual vitamin C usage.

The instability of vitamin C leads to problems in laboratory analysis , and vitamin C is not routinely measured in dialysis practice.

Concerns about oxalosis need to be vigorously addressed, but if vitamin C is demonstrated to be safe, its more active use could lead to reduction of iron burden, more efficient erythropoiesis and alleviation of some of the scorbutic symptoms seen in HD patients.

Mild renal failure as a marker for cardiovascular mortality

Eur Heart J. 2007 Feb;28(4):478-83. Epub 2007 Jan 12.

The glomerular filtration rate in an apparently healthy population and its relation with cardiovascular mortality during 10 years.

• Van Biesen W,
• De Bacquer D,
• Verbeke F,
• Delanghe J,
• Lameire N,
• Vanholder R.

Department of Internal Medicine, Renal Division, University Hospital Ghent, De Pintelaan 185, 9000 Ghent, Belgium.

AIMS: Moderate-to-severe chronic renal failure is an established risk factor for cardiovascular disease and mortality.

However, most studies have been performed in selected populations and the impact of very small decrements of renal function on long-term cardiac morbidity and mortality has not yet been established.

Also, the cut-off level of glomerular filtration rate (GFR) from which cardiovascular risk increases has not exactly been established. This study wants to address these questions.

METHODS AND RESULTS: Ten year follow-up of a representative population-based cohort comprised 8913 randomly selected, apparently healthy participants. Participants were randomly drawn from Belgian voting lists. Cardiovascular risk factors were noted.

Serum creatinine values were corrected to isotope dilution mass spectrometry standard, and GFR was calculated using the recently modified 'modification of diet in renal disease' equation.

Participants were followed for 10 years, and cause-specific death was registered by analysis of death certificates.

The probability to die from all causes or from cardiovascular causes during the 10 year follow-up period increased in each quartile of GFR, even after correction for different other comorbid conditions.

CONCLUSION: Even mild renal failure is an independent risk factor for cardiovascular mortality within 10 years in an apparently healthy unselected population.

This detrimental effect starts already at a relatively high GFR of 90 mL/min/1.73 m(2) and remains present after correction for other established cardiovascular risk factors.

----------------------------
A similar study published earlier
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Kidney Int. 2002 Oct;62(4):1402-7.

Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study.

• Henry RM,
• Kostense PJ,
• Bos G,
• Dekker JM,
• Nijpels G,
• Heine RJ,
• Bouter LM,
• Stehouwer CD.

Institute for Research in Extramural Medicine, Department of Clinical Epidemiology and Biostatistics, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

BACKGROUND: Cardiovascular mortality is extremely high in end-stage renal disease. Cardiovascular mortality risk also is increased in selected (high-risk) individuals with mild to moderate impairment of renal function.

It is not clear whether a similar association exists in the general population and, if so, through what mechanisms. We investigated the association of renal function with all-cause and cardiovascular mortality in a population-based cohort and explored potential mechanisms underlying any such relationship.

METHODS: An age-, sex-, and glucose-tolerance-stratified sample (N = 631) of a population-based cohort aged 50 to 75 years was followed prospectively. After up to 10.2 years of follow-up, 117 subjects had died (50 of cardiovascular causes).

At baseline, renal function was estimated by the serum creatinine level, the Cockcroft-Gault formula and Levey's equation.

RESULTS: At baseline, the mean age was 64 +/- 7 years, 48% were men, 55% had hypertension, and 27% (by design) had type 2 diabetes.

• Serum creatinine was 91.7 +/- 19.0 micromol/L;
  
• creatinine clearance as estimated by the Cockroft-Gault formula was 72.5 +/- 13.7 mL/min/1.73 m(2),
  
• glomerular filtration rate (GFR) estimated by Levey's equation was 67.8 +/- 12.1 mL/min/1.73 m(2).
  

Renal function was inversely associated with all-cause and with cardiovascular mortality.

Relative risks (95% confidence intervals) were

• 1.08 (1.04 to 1.13) and 1.11 (1.07 to 1.16) per 5 micromol/L increase of serum creatinine;
• 1.07 (0.98 to 1.17) and 1.15 (1.01 to 1.31) for each decrease of 5 mL/min/1.73 m(2) creatinine clearance;
  
• 1.15 (1.05 to 1.26) and 1.26 (1.12 to 1.42) for each decrease of 5 mL/min/1.73 m(2) of GFR.
  

These associations remained after adjusting for age, sex, glucose tolerance status, hypertension, prior cardiovascular disease, low-density lipoprotein cholesterol, homocysteine, (micro)albuminuria, von Willebrand factor, soluble vascular adhesion molecule-1 and C-reactive protein.
Analyses in diabetic and hypertensive subjects gave similar results.

CONCLUSION: Mild to moderate loss of renal function is strongly associated with an increased risk of cardiovascular mortality.
The mechanism behind this association is unclear but does not appear to involve common risk factors such as hypertension, diabetes or hyperhomocysteinemia.

Estimation of renal function by relatively simple methods therefore may be a valuable tool for cardiovascular risk assessment over and above that provided by conventional risk factors.

Our results were obtained in a general middle-aged to elderly population, and thus have broad applicability.

Hypertension biomarkers

Hypertension. 2007 Mar;49(3):432-8. Epub 2007 Jan 22.

Multiple biomarkers and the risk of incident hypertension.

• Wang TJ,
• Gona P,
• Larson MG,
• Levy D,
• Benjamin EJ,
• Tofler GH,
• Jacques PF,
• Meigs JB,
• Rifai N,
• Selhub J,
• Robins SJ,
• Newton-Cheh C,
• Vasan RS.

Framingham Heart Study, Framingham, Mass, USA. tjwang@partners.org

An understanding of mechanisms underlying the development of essential hypertension is critical for designing prevention and treatment strategies. Selected biomarkers may be elevated before the onset of hypertension, but previous studies are limited by cross-sectional designs or a focus on single biomarkers.

We prospectively studied 1456 nonhypertensive individuals who had baseline measurement of 9 biomarkers:

1. C-reactive protein (inflammation);
   
2. fibrinogen (inflammation and thrombosis);
   
3. plasminogen activator inhibitor-1 (fibrinolytic potential);
   
4. aldosterone, renin, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptide (neurohormonal activity);
   
5. homocysteine (renal function and oxidant stress);
   
6. urinary albumin/creatinine ratio (glomerular endothelial function).
   

Incident hypertension, defined as blood pressure > or =140/90 mm Hg or antihypertensive therapy, developed in 232 participants over a mean follow-up of 3 years.

After adjustment for clinical risk factors, the biomarker panel was significantly associated with incident hypertension (P=0.002).

Three (of 9) biomarkers were significantly related to incident hypertension on backward elimination (multivariable-adjusted odds ratios, per SD increment in biomarker):

1. C-reactive protein (1.26; 95% CI: 1.05 to 1.51),
   
2. plasminogen activator inhibitor-1 (1.28; 95% CI: 1.05 to 1.57),
   
3. urinary albumin/creatinine ratio (1.21; 95% CI: 1.02 to 1.43).
   

The incidence of hypertension was 4.5, 6.4, and 9.9 per 100 person years for participants with 0, 1, and > or=2 elevated biomarkers, respectively (elevation defined as > or =1 SD above the mean).

The threshold of > or =2 elevated biomarkers for predicting hypertension was associated with high specificity (0.92) but low sensitivity (0.15).

Biomarkers of inflammation, reduced fibrinolytic potential, and low-grade albuminuria are jointly associated with the incidence of hypertension.
These data support the premise that abnormalities in multiple biological pathways antedate the onset of overt hypertension.

No more heplock??? its citlock now.

Nephrol Dial Transplant. 2007 Feb;22(2):477-83. Epub 2006 Oct 2.

Trisodium citrate 4%--an alternative to heparin capping of haemodialysis catheters.

* Lok CE,
* Appleton D,
* Bhola C,
* Khoo B,
* Richardson RM.

Department of Medicine, Division of Nephrology, The Toronto General Hospital, 11 EN-216, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada. charmaine.lok@uhn.on.ca.

BACKGROUND: Central venous catheters (CVCs) continue to be used at a high rate for dialysis access and are frequently complicated by thrombus-related malfunction. Prophylactic locking with an anticoagulant, such as heparin, has become standard practice despite its associated risks. Trisodium citrate (citrate) 4% is an alternative catheter locking anticoagulant.

METHODS: The objective was to prospectively study the clinical effectiveness, safety and cost of citrate 4% vs heparin locking by comparing rates of CVC exchanges, thrombolytic use (TPA) and access-associated hospitalizations during two study periods: heparin period (HP) (1 June 2003-15 February 2004) and Citrate Period (CP) 15 March-15 November 2004. Incident catheters evaluated did not overlap the two periods.

RESULTS: There were 176 CVC in 121 patients (HP) and 177 CVC in 129 patients (CP).
The event rates in incident CVC were:

1. CVC exchange 2.98/1000 days (HP) vs 1.65/1000 days (CP) (P = 0.01);
   
2. TPA use 5.49/1000 (HP) vs 3.3/1000 days (CP) (P = 0.002);
   
3. hospitalizations 0.59/1000 days (HP) vs 0.28/1000 days (CP) (P = 0.49).
   
4. longer time from catheter insertion to requiring CVC exchange (P = 0.04) and TPA (P = 0.006) in the citrate compared with the heparin lock group.
   

Citrate locking costs less than heparin locking but a formal economic analysis including indirect costs was not done.

CONCLUSION:

• Citrate 4% has equivalent or better outcomes with regards to catheter exchange, TPA use and access-related hospitalizations compared with heparin locking.
  
• It is a safe and less expensive alternative.
  

Randomized trials comparing these anticoagulants with a control group would definitively determine the optimal haemodialysis catheter locking solution.

Vasopressin in ESRD - Maintainance HD patients.

Kidney Int. 2007 Feb;71(4):318-24. Epub 2006 Sep 27.

Vasopressin administration facilitates fluid removal during hemodialysis.

• van der Zee S,
• Thompson A,
• Zimmerman R,
• Lin J,
• Huan Y,
• Braskett M,
• Sciacca RR,
• Landry DW,
• Oliver JA.

1Department of Medicine, Columbia University, New York, New York, USA.

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal.

To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase.

We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed.

Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription.

We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024).

Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01).

Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid.

Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.