[Considerations when using creatinine as a measure of kidney function]. / Aandachtspunten bij het gebruik van creatinine als maat voor de nierfunctie.

Reported serum creatinine concentrations can sometimes vary considerably, even when the renal function does less so or even not. This variation is partly due to true changes in actual serum concentration, and partly due to interferences in the measurement technique, thus not reflecting a true change in concentration. Increased or decreased endogenous creatinine production, ingested creatinine sources through meat eating or certain creatine formulations, and interference by either browning of chromogenic substances in Jaffe measurement techniques or promotors and inhibitors of enzymatic reaction methods do play a role. Reliable serum creatinine measurements are needed for renal function estimating equations. In screening circumstances and daily practice, chronic kidney disease staging is based on these estimated glomerular filtration rate values. Given the possible influences on reported serum creatinine concentrations, it is important for health care workers to remain critical when interpreting outcomes of renal function estimating equations and to not see every reported result based on an equation as a true reflection of renal function.

Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33).

AIM/HYPOTHESIS: Arginine vasopressin (AVP), the hormone important for maintaining fluid balance, has been shown to cause kidney damage in rodent models of diabetes. We investigated the potential role of AVP in the natural course of kidney function decline in diabetes in an epidemiological study. METHODS: Plasma copeptin, a surrogate for AVP, was measured in baseline samples from patients with type 2 diabetes treated in primary care and included in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort. RESULTS: Samples from 1,328 patients were available; 349 were analysed separately because they used renin-angiotensin-aldosterone system inhibition (RAASi), which influences albumin/creatinine ratio (ACR) and estimated (e)GFR. In the other 979 patients (46% men, age 68 years [58-75], ACR 1.8 mg/mmol [0.9-5.7], eGFR 67 ± 14 ml min(-1) 1.73 m(-2)) baseline copeptin (5.3 pmol/l [3.2-9.5]) was significantly associated with log e [ACR] and eGFR, even after adjustment for sex, age and risk factors for kidney function decline (standardised [std] ß 0.13, p < 0.001, std ß -0.20, p < 0.001 respectively). Follow-up data were available for 756 patients (6.5 years [4.1-9.6]). Baseline copeptin was associated with increase in ACR (std ß 0.09, p = 0.02), but lost significance after adjustment (std ß 0.07, p = 0.08). Copeptin was associated with a decrease in eGFR after adjustment (std ß -0.09, p = 0.03). The strength of the association of copeptin with change in eGFR was stronger than that of established risk factors for kidney function decline (e.g. BMI, HbA1c). In patients who used RAASi there was a significant association between baseline copeptin and ACR and eGFR, but not with change in ACR and eGFR. CONCLUSIONS/INTERPRETATION: In patients with diabetes not using RAASi a higher baseline copeptin concentration is significantly associated with higher baseline ACR and lower eGFR values and with a decline in eGFR during follow-up. This last association is independent of, and stronger than, most traditional risk factors for kidney function decline.

Glycaemic control and the risk of mortality in elderly type 2 diabetic patients (ZODIAC-20).

AIMS: Studies on macrovascular consequences of glucose control in elderly patients (>75 years) with type 2 diabetes mellitus (T2DM) are lacking. The present study aimed to investigate the relationship between HbA(1c) and mortality in this specific population. METHODS: Between 1998 and 1999, 374 primary care patients with T2DM aged older than 75 years participated in the Zwolle Outpatient Diabetes project Integrating Available Care study, a prospective observational study. Early 2009, data on mortality were collected. Updated means for annually measured HbA(1c) values were calculated after a follow-up time of 10 years. Updated mean HbA(1c) was used as a time-dependent covariate in a Cox proportional hazard model. Main outcome measures were all-cause and cardiovascular disease (CVD) mortality. Analyses were performed in strata according to diabetes duration (<5, 5-11 and ≥11 years). RESULTS: In the group with a diabetes duration <5 years, an increase of 1% in the updated mean HbA(1c) level was associated with an increase in all-cause and CVD mortality risk of 51% (95% CI 17-95%) and 72% (95% CI 19-148%), respectively. Glycaemic control was not related to mortality for patients with a diabetes duration ≥5 years. CONCLUSION: Poor glycaemic control is related to increased all-cause and CVD mortality in patients >75 years with T2DM of short duration (<5 years). DISCUSSION: Because of the observational study design, our results should be interpreted with caution. Nevertheless, they are suggestive that improving glycaemic control may be beneficial in elderly patients with T2DM, especially in those with recently diagnosed T2DM. Randomised-controlled trials are necessary to investigate whether this holds true.

eGFR and creatinine clearance in relation to metabolic changes in an unselected patient population.

BACKGROUND: It is widely assumed that moderate to severe renal failure (creatinine clearance <60 ml/min; or an MDRD-4 (Modification of Diet in Renal Disease equation) <60 ml/min/1.73 m(2)) is associated with metabolic changes, often needing further assessment and treatment. We investigated whether such abnormalities are already present at earlier stages of kidney disease, as assessed by 24-hour urine sampling and MDRD-4 calculation. METHODS: A select, retrospective cohort study was conducted. Creatinine clearance was measured by collecting 24-hour urines. The individual eGFRs were calculated with the MDRD-4 formula and patients were then divided by renal function category (<15, 15-30, 30-45, 45-60, 60-90, >90 ml/min(/1.73 m(2))). Per clearance category the number of people with anaemia, hypokalaemia, uraemia and hyperphosphataemia was evaluated. RESULTS: The median creatinine clearance rate was 67.3 ml/min (quartiles: 42.9-95.8) versus a median MDRD-4-eGFR of 51.6 ml/min/1.73 m(2) (35.8-67.7). Anaemia, hyperkalaemia, hypocalcaemia, and uraemia were found to be present at higher levels of creatinine clearance rate and eGFR than previously reported (p<0.0005). This increased prevalence was more pronounced in elderly subjects, particularly with respect to anaemia (OR 2.71 and 2.02 for MDRD-4 and creatinine clearance respectively, p<0.0005). The same holds for the proportion with uraemia (OR 1.85, p<0.0005) and hypocalcaemia (OR 1.97, p=0.011) for MDRD-4. CONCLUSION: Metabolic changes in an in- and outpatient hospital population are present at earlier stages than was stated in recent guidelines, especially when creatinine clearance levels are used as indicators. This might have implications for testing and treatment of patients with suspected kidney disease and/or loss of renal function.