Cystatin C improves the diagnosis and stratification of chronic kidney disease, and the estimation of glomerular filtration rate in diabetes.

AIMS: Estimation of glomerular filtration rate (GFR) is recommended to diagnose and stratify chronic kidney disease (CKD). Can cystatin-C (cysC) assay improve the results in diabetic patients? METHODS: In 124 diabetic patients with a wide range of GFR, as determined by 51Cr-EDTA clearance (i-GFR), we estimated 'e-GFR' by: the recommended Cockcroft-Gault (CG) formula and Modification of Diet in Renal Disease (MDRD) study equation; the new Mayo Clinic quadratic (MCQ) equation; the recently proposed composite estimation including both serum creatinine and cysC; and a simplified approach dividing the MDRD by cysC if less than 1.10mg/L. RESULTS: The highest diagnostic accuracy (receiver operating characteristic [ROC] curves) and the highest proportions of well-stratified patients were obtained by cysC and the MDRD which, however, underestimated i-GFR for patients without CKD (-17%, P<0.001). The CG overestimated GFR in KDOQI stages 1 and 2, ignored stage 5 and was the least accurate. The MCQ equation overrepresented stage 2, overestimating GFR at this stage (+23%, P<0.005). The composite estimation (54.7+/-27.0mL per minute 1.73m(2)) correlated best with i-GFR (56.1+/-35.3; r=0.90, P<0.001), and did not significantly differ from it across the entire population and within each Kidney Disease Outcome Quality Initiative (KDOQI) stage but was also biased (Bland-Altman procedure). Simply dividing the MDRD by cysC ifless than1.10mg/L produced a comparable performance and eliminated the bias. CONCLUSION: The recommended creatinine-based estimations of GFR need to be improved. CysC assay helps in the diagnosis and stratification of CKD and leads to better estimates of GFR in diabetic patients without any substantial increase in complexity.

Air displacement plethysmography can detect moderate changes in body composition.

OBJECTIVES: To determine the sensitivity of air displacement plethysmography (APD) for evaluation of changes in body composition in normal subjects. DESIGN: Comparison of measurements with and without oil or water loads. SUBJECTS AND METHODS: Ten healthy volunteers were analyzed, without and with 1 l and 2 l of oil or water. The measured and true changes in fat mass and fat-free mass were compared by paired t-tests. A correlation study and a Bland & Altman procedure was performed on the 60 measurements of adiposity changes in 30 subjects carrying 0.5 l (n=8 x 2), 1 l (n=10 x 2) and 2 l (n=12 x 2) oil and water loads. RESULTS: Fat-free mass increased when the 10 subjects were carrying water. When they carried oil, fat mass increased, however, a approximately 0.5 kg increase of fat-free mass was also detected. Two liters loads led to distinct changes: +1.49+/-0.59 kg fat and +0.50+/-0.60 kg fat-free with oil and +0.37+/-0.57 kg fat and +1.70+/-0.56 kg fat-free with water (both P<0.001). Mixed loads (+1 l oil and 1 l water) led to detect +0.85+/-0.48 kg fat and +1.09+/-0.45 kg fat-free (both P<0.005 vs without load). For the 30 subjects analyzed thrice, measured changes in fat and fat-free mass were slightly underestimated (-15%, NS) but correlated with the true changes. Measured changes in adiposity were correlated with the true changes, with no bias as indicated by the Bland & Altman procedure. CONCLUSION: APD detects approximately 2 kg changes in fat or fat-free mass in small populations.

How to better systematize the diagnosis of neuropathy?

Two attitudes can be proposed, one consisting of making a diagnosis of neuropathy, the other seeking to grade the stage that it has reached in order to give a prognosis and above all determine the right way in which to educate the patient. In order to do this, it is important for the diagnosis to be thorough. It should be based both on listening to what the patient has to say and examining him/her. It is vital to listen to the patient because the warning signs are discreet, yet very evocative, and they will be a great help in making a positive diagnosis. They should not be confused with signs of arterial damage. They should then be interpreted by means of clinical examination and the tools that are available, i.e. essentially monitoring the osteo-tendinous reflexes and sensory signs. The sensory signs can only be studied with high-quality instruments, i.e. either a monofilament of proven technical quality and that should be used with care in line with good clinical practice recommendations, or by using a graduated tuning fork, or a neuroesthesiometer which will make it possible to obtained graduated responses, not simply binary responses of the "yes/no" variety. A whole series of scores have been put forward combining both functional and physical signs, making it possible to try to quantify the stage reached and the extent of the neuropathy. It is only by using a thorough and regularly applied routine that we can progress to establishing a better prognosis and providing a better educational service for the patient.

A simplified Cockcroft-Gault formula to improve the prediction of the glomerular filtration rate in diabetic patients.

AIM: The National Kidney Foundation recommends stratification of renal failure into moderate (Glomerular Filtration Rate: GFR = 30-60 mL/min/1.73 m2), severe (15-30) or terminal (<15) using the Cockcroft-Gault (CG) or the Modification of Diet in Renal Disease (MDRD) equations. We studied the biases in these methods in an attempt to improve the standard CG (MCG) and devise a strategy for stratification. METHODS: GFR was measured by 51Cr-EDTA clearance in 200 diabetic patients: 100 (Group 1: study of concordance) before 2003 and 100 thereafter (Group 2: validation of MCG). The CG was modified by replacing body weight by its mean value: 76. RESULTS: In group 1, the recommended equations only correctly stratified 50 patients. The CG, not the MDRD, underestimated GFR if BMI was normal, and overestimated it in obese patients. In group 2, the MCG was well correlated with GFR and not biased by weight. Over the whole population, the MCG and MDRD were more accurate for the diagnosis of moderate and severe renal failure. The MDRD showed the lowest differences with GFR, except if GFR > 60, where the MCG performed better. All formulae overestimated low GFR, the MDRD also underestimated high GFR. The best stratification (147/200) was obtained using the MCG if creatininemia < 120 micromol/l and the MDRD if creatininemia > or =120 micromol/l. CONCLUSION: The CG is biased by weight, the MCG corrects this. The more accurate MDRD cannot be used in all patients as it underestimates high GFR. The best stratification was obtained using the MCG at low and the MDRD at high creatininemia.

[Pathogenic links between Kikuchi's disease and lupus: a report of three new cases]. / Liens physiopathologiques entre maladie de Kikuchi et lupus: à propos de trois nouvelles observations.

INTRODUCTION: Histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto's disease is a rare anatomoclinical entity whose etiology remains unknown. It is mainly reported in young adult female, presenting with cervical lymphadenopathies, fever and asthenia. The diagnosis is based on the histological examination of a lymph node biopsy. The disease course is usually uneventful, but sometimes Kikuchi-Fujimoto's disease can reveal or evolve into a cutaneous or a systemic lupus. EXEGESIS: We report three new cases of Kikuchi's disease: the first one mimicked a systemic lupus, the second one was associated with a lupus-like rash, and a the last one was a severe case with hemophagocytic syndrome and a primo-infection with Epstein-Barr virus revealing a systemic lupus erythematosus. CONCLUSION: Clinical and biological follow-up of patients presenting with Kikuchi's disease is necessary to look for an association with a lupus. We discuss the pathogenic links between Kikuchi's disease and lupus.

Emphysematous cystitis.

We present a case of emphysematous cystitis in a diabetic patient with a poor glycemic control in the context of alcoholic chronic pancreatitis. A 62-year-old woman was admitted to the emergency department after being found on floor with confusion and vomiting. The clinical examination was unremarkable except she was undernourished, agitated and presented an hepatomegaly. Urine contained 5.104 leukocytes/mm3 and culture grew Escherichia coli, 10(7) Colony Forming Unit/ml. Abdominal plain film showed gas shadows along the wall of urinary bladder. CT scan of the pelvis confirmed the presence of gas, and diffuse thickening of the urinary bladder wall. A Foley catheter was placed and the patient was treated with antibiotics for 6 weeks. She was also treated with insulin, rehydratation, vitamin B1 and B6, and pancreatic enzyme replacement. Emphysematous cystitis is defined by the presence of gas in the urinary bladder wall. It complicates urinary tract infections especially in diabetic patients but other disabled general medical conditions may be present. Because this relatively uncommon disease may present with fairly nonspecific findings, the diagnosis is often made incidentally on X-rays. However, as early diagnosis and treatment improve the outcome, a high index of suspicion for unusual presentations is warranted. Every diabetic patient with a urinary tract infection who seems to be severely ill should have an abdominal X-ray as a minimal screening tool to detect emphysematous complications.

Resting energy expenditure in uremic, diabetic, and uremic diabetic subjects.

We compared Harris and Benedict [H & B; Harris, J. A., & Benedict, F. G. (1919). A biometric study of basal metabolism in man. Washington, DC: Carnegie Institution of Washington. p. 279.] predicted resting energy expenditure (REE) to values measured by indirect calorimetry in normal, uremic, diabetic, and uremic diabetic subjects. Predicted REE were overestimated (+9.2%, P<.005) in uremic subjects, and underestimated (-8.5%, P<.0001) in diabetic subjects. Uremic diabetic subjects were submitted to the opposite influences of diabetes and uremia on REE. Differences in body composition (lower fat-free mass in uremia and higher fat-free mass in diabetes) played a major role in these influences. In uremic diabetic subjects, predicted REE seemed well fitted to measured REE (biases <2%), but they were less correlated, and limits of agreement between predicted and measured REE were large. Although their mean REE seems normal, prediction by the H&B equation leads to important individual errors in uremic diabetic subjects: direct measurement of energy expenditure by indirect calorimetry may be helpful to precise the adequate energy content of a diet for these subjects.

Insulin therapy and body weight, body composition and muscular strength in patients with type 2 diabetes mellitus.

Aims. To determine the progression of body weight (BW) and body composition (BC) in patients with type 2 diabetes mellitus (T2D) on insulin therapy and the consequences on muscle strength (MS) as a reflect of free fat mass increases. Research design and methods. We analysed BC using air displacement plethysmography and MS by hand grip dynamometry in 40 T2D before and after three (M3) and six months (M6) of insulin therapy. Results. at baseline HbA1c was 9.76 +/-1.6% and BW was stable with fat mass (FM) 28 +/- 10.7 kg; and fat free mass (FFM) 52.4 +/- 11 kg; at M6, HbA1c improved to 7.56 +/- 0.8%; insulin doses tended to increase. BW gain at M6 was + 3.2 +/- 4.2 kg and with an increase of only 25% by M3; it was composed of FM, whereas FFM was unchanged. MS did not increase on insulin therapy. Conclusions. In T2D, BW gain was composed exclusively of FM with no improvement in MS.

Bone loss in diabetic patients with chronic kidney disease.

OBJECTIVE: We investigated whether loss of bone is detectable during follow-up of diabetic patients with chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: In 40 initially non-dialysed diabetic patients with CKD (isotopic glomerular filtration rate < 60 ml/min/1.73 m(2) or albumin excretion rate > 30 mg/24 h), body composition (DEXA scan) and glomerular filtration rate (GFR determined from (51)Cr-EDTA clearance) were measured at a 2-year interval, and compared by paired t-tests. RESULTS: The 40 patients, mainly with Type 2 diabetes (n = 28), were men (n = 28), aged 65 +/- 11 years, with diabetes duration 18 +/- 11 years. GFR was initially 38.0 (range 8-89) ml/min/1.73 m(2). CKD progressed during follow-up: eight started haemodialysis and GFR declined in the 32 others (P < 0.05 vs. initial). T-scores for total body (initial -0.61 +/- 1.11, final -1.11 +/- 1.40; P < 0.001) and femoral neck (initial -1.88 +/- 0.15, final -2.07 +/- 0.15; P < 0.05) declined. Ten patients were osteopaenic at baseline (no osteoporosis), whereas most were osteopaenic (n = 21, P < 0.05) and five were osteoporotic at final assessment. The 16 patients who became osteopaenic or osteoporotic during follow-up did not differ from the others for the type of diabetes, age, GFR, albumin excretion rate, HbA(1c), GFR reduction and the requirement for dialysis during follow-up. They were all men (P < 0.01 by chi-squared test), with reduced initial total body T-score (-1.20 +/- 0.82, others -0.32 +/- 1.13; P < 0.05) and a lower body mass index (24.6 +/- 4.3; others 27.7 +/- 4.3; P < 0.05). CONCLUSION: Bone loss, especially in the femoral neck, is progressive in diabetic patients with CKD.

Lower plasma triglycerides are associated with increased need for insulin requirement in poorly controlled Type 2 diabetic patients.

AIMS: To identify factors associated with insulin requirement in Type 2 diabetic patients, and to examine the significance of a normal plasma triglyceride level. METHODS: One hundred and three poorly controlled (HbA1c = 9.4 +/- 1.9%) Type 2 diabetic patients initially not treated with insulin were followed up for 5 years. Insulin was administered if HbA1c > 8% despite maximal oral anti-diabetic treatment and bodyweight control. Variables were compared between insulin requiring and non-insulin-treated patients using unpaired t-tests. The outcomes of initially normotriglyceridaemic (< 1.7 mmol/l) and hypertriglyceridaemic patients were compared using unpaired t-tests, and a survival analysis (Cox proportional hazards model). RESULTS: Sixty-three patients were transferred to insulin. They were 5 years older (P = 0.004), with a 3-year longer duration of their diabetes (P = 0.03), a 1.2% higher HbA1c (P = 0.002), and 50% lower triglyceride levels (P = 0.02) than the others. The survival analysis showed that a long duration of diabetes, a high HbA1c, and a normal triglyceride level were associated with the need for insulin; the effect of normotriglyceridaemia was significant in the most poorly controlled (HbA1c > 9.5%) patients (relative risk: 2.35, 95% confidence interval: 1.16-5.52, P = 0.016). The 46 normotriglyceridaemic patients were leaner (P = 0.0004) and had lower C-peptide levels (P = 0.0008) than the others. Despite similar diabetes duration and HBA1c, more were transferred to insulin (normotriglyceridaemic: 71%, hypertriglyceridaemic: 52%, P = 0.03). CONCLUSION: A normal triglyceride level is associated with a need for insulin in poorly controlled Type 2 diabetes.

Body composition in diabetic subjects with chronic kidney disease: interest of bio-impedance analysis, and anthropometry.

BACKGROUND/AIMS: Lean body mass (LBM) is reduced in uremia, but this has not been reported in diabetic nephropathy. SUBJECTS AND METHODS: We compared predicted % LBM to DEXA measurements in 10 non-diabetic uremic, 10 non-uremic diabetic and 10 uremic diabetic subjects matched for age, gender and BMI. We also measured % LBM by anthropometry, bio-impedance analysis (BIA) and compared them with DEXA in 49 diabetic subjects with a wide range of renal failure. The results were compared and a Bland & Altman procedure was performed. Associations between glomerular filtration rate (GFR) and % LBM were tested. RESULTS: In matched groups, predicted % LBM values were overestimated in non-diabetic uremic subjects, and underestimated in non-uremic diabetic subjects. In uremic diabetic subjects, the error was intermediary. As compared to DEXA (% LBM: 69.0 +/- 7.1%), measurement of % LBM by anthropometry (71.4 +/- 8.0%, p < 0.05) and BIA (67.2 +/- 7.6%, p < 0.05) were biased in the 49 diabetic subjects. The mean of anthropometric and BIA (Ant+BIA) were similar to DEXA results (69.3 +/- 6.8%, p = 0.64), with best correlation coefficients and Bland & Altman plots. GFR was correlated to % LBM assessed by DEXA, BIA and Ant+BIA. CONCLUSION: In diabetic subjects with chronic kidney disease, LBM should be measured, rather than predicted. A good evaluation is possible, even without DEXA.