Henrik Hadimeri

Risk factors for the development of albuminuria and renal impairment in type 2 diabetes—the Swedish National Diabetes Register (NDR)

BACKGROUND The aim of this study was to identify clinical risk factors associated with the development of albuminuria and renal impairment in patients with type 2 diabetes (T2D). In addition, we evaluated if different equations to estimate renal function had an impact on interpretation of data. This was done in a nationwide population-based study using data from the Swedish National Diabetes Register. METHODS Three thousand and six hundred sixty-seven patients with T2D aged 30-74 years with no signs of renal dysfunction at baseline (no albuminuria and eGFR >60 mL/min/1.73 m(2) according to MDRD) were followed up for 5 years (2002-2007). Renal outcomes, development of albuminuria and/or renal impairment [eGFR < 60 mL/min/1.73 m(2) by MDRD or eCrCl > 60 mL/min by Cockgroft-Gault (C-G)] were assessed at follow-up. Univariate regression analyses and stepwise regression models were used to identify significant clinical risk factors for renal outcomes. RESULTS Twenty percent of patients developed albuminuria, and 11% renal impairment; thus, ~6-7% of all patients developed non-albuminuric renal impairment. Development of albuminuria or renal impairment was independently associated with high age (all P < 0.001), high systolic BP (all P < 0.02) and elevated triglycerides (all P < 0.02). Additional independent risk factors for albuminuria were high BMI (P < 0.01), high HbA1c (P < 0.001), smoking (P < 0.001), HDL (P < 0.05) and male sex (P < 0.001), and for renal impairment elevated plasma creatinine at baseline and female sex (both P < 0.001). High BMI was an independent risk factor for renal impairment when defined by MDRD (P < 0.01), but low BMI was when defined by C-G (P <  0.001). Adverse effects of BMI on HbA1c, blood pressure and lipids accounted for ~50% of the increase risk for albuminuria, and for 41% of the increased risk for renal impairment (MDRD). CONCLUSIONS Distinct sets of risk factors were associated with the development of albuminuria and renal impairment consistent with the concept that they are not entirely linked in patients with type 2 diabetes. Obesity and serum triglycerides are semi-novel risk factors for development of renal dysfunction and BMI accounted for a substantial proportion of the increased risk. The equations used to estimate renal function (MDRD vs. C-G) had an impact on interpretation of data, especially with regard to body composition and gender.

Low-dose atorvastatin in severe chronic kidney disease patients: a randomized, controlled endpoint study.

Objective. There have been no endpoint studies with statins for patients with severe renal failure. The purpose of this prospective, open, randomized, controlled study was to investigate whether atorvastatin (10 mg/day) would alter cardiovascular endpoints and the overall mortality rate of patients with chronic kidney disease stage 4 or 5 (creatinine clearance < 30 ml/min). Material and methods. The study subjects comprised 143 patients who were randomized either to placebo (controls; n=73; mean age 69.5 years) or to treatment with atorvastatin (n=70; mean age 67.9 years). The patients included were either non-dialysis (n=33), haemodialysis (n=97) or peritoneal dialysis (n=13) patients. Analysis focused on the primary endpoints of all-cause mortality, non-lethal acute myocardial infarction, coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty. Statistical analysis for endpoint data was mainly by intention-to-treat. Results. Primary endpoints occurred in 74% of the subjects. There was no difference in outcome between the control and atorvastatin groups. The 5-year endpoint-free survival rate from study entry was ≈20%. Atorvastatin was withdrawn in ≈20% of patients due to unacceptable side-effects. In the atorvastatin group, low-density lipoprotein (LDL) cholesterol was reduced by 35% at 1 month and then sustained. The controls showed a progressive reduction in LDL cholesterol until 36 months. Conclusions. Although atorvastatin reduced total and LDL cholesterol effectively it was not beneficial regarding the long-term outcomes of cardiovascular endpoints or survival. In contrast to other patient groups, patients with severe chronic kidney disease, especially those on dialysis, seem to derive limited benefit from this lower dose of atorvastatin.

A study of clinical complications and risk factors in 1001 native and transplant kidney biopsies in Sweden

Background In Sweden, native and transplant kidney biopsies are usually performed in major renal medical centers. Purpose To clarify risk factors in native and transplant kidney biopsies to improve patient safety. Material and Methods A total of 1001 biopsies (in 352 women and 565 men) were included. The median age was 54 years (range, 16–90 years). Data were derived from 826 native kidney biopsies (640 prospective and 186 retrospective) and 175 transplant kidney biopsies (170 prospective and 5 retrospective). Various factors and complications were registered while performing native and transplant kidney biopsies, focusing on major (e.g. blood transfusions, invasive procedures) and minor complications. The prospective protocol was used at six centers and at one center data were obtained retrospectively. Results Women were at greater risk of overall complications than men (12.2% vs. 6.5%; P = 0.003; odds ratio [OR], 2.0; confidence interval [CI], 1.3–3.1) as well as of major complications (9.6% vs. 4.5%; P = 0.002; OR, 2.2, CI 1.3–3.7). Major complications occurred more commonly after biopsies from the right kidney, in women than in men (10.8% vs. 3.1%; P = 0.005; OR, 3.7; CI, 1.5–9.5), and in patients with lower BMI (25.5 vs. 27.3, P = 0.016) and of younger age (45 years vs. 52.5 years; P = 0.001). Lower mean arterial pressure in transplant kidney biopsies indicated a risk of major complications (90 mmHg vs. 98 mmHg; P = 0.039). Factors such as needle size, number of passes, serum creatinine, and eGFR did not influence complication rates. Conclusion The present findings motivate greater attention being paid to the risk of major side-effects after right-side biopsies from women’s kidneys, as well as after biopsies from younger patients and patients with lower BMI.

A new safety device for hemodialysis

Accidental venous needle dislodgement during hemodialysis may cause serious bleeding including a sometimes fatal outcome. The venous pressure gauge of the dialysis monitor does not react when dislodgement occurs. A sensor patch put as an adhesive over the venous needle puncture site connected to an alarm unit by an optic fiber has been clinically tested in 5 dialysis departments. A small amount of blood on the sensor activates a light and sound alarm. A simple questionnaire was filled out by the nurses at each dialysis concerning their feeling of safety when the new device was used. Forty‐one patients, mean age 65 years, have tested the new safety device. Two hundred test dialyses were studied, after exclusion of 13 tests. One hundred seventy‐nine tests reacted positively on blood. In another 6 dialyses, a warning light appeared on the alarm unit indicating a failure in the sensor patch. Thus, the alarm functioned in 92.5% of all tests. After a small modification of the sensor patches there were only 2 dialyses (2/71) without an activated alarm on blood, i.e., 97.2% positive alarm reactions. The answers of the nurses indicated that they had an increased feeling of safety when using the new safety device, with a mean value of 3.4 points on a visual scale from 0 to 5 where 5 meant very much increased safety. In a situation when the dialysis monitors today do not react on bleedings from venous needle dislodgements, the new alarm safety device fulfils a known shortage in routine dialysis safety. In situations where supervision during a dialysis session may be insufficient as, for example, in home hemodialysis and self‐care dialysis or in other situations when the patient is sleeping, the device may be life saving.

Safety and efficacy of atorvastatin in patients with severe renal dysfunction

Objective. To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a glomerular filtration rate of <30 ml/min. Material and methods. This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. Results. The follow-up period was a mean of 20±14.4 months (range 1–36 months) for those on atorvastatin versus 22±12.7 months (range 0.5–36 months) for the controls. Compared with baseline values, patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4 mmol/l; −23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; −35%; p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8 mmol/l). The controls had significantly reduced levels of total cholesterol at Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the controls, the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1–30. Fifteen patients (21%) stopped taking their medication as they could not tolerate the side-effects, the most frequent complaints being gastrointestinal discomfort and headache. Conclusion. Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.

Ongoing treatment with renin-angiotensin-aldosterone-blocking agents does not predict normoalbuminuric renal impairment in a general type 2 diabetes population☆

AIM To examine the prevalence and the clinical characteristics associated with normoalbuminuric renal impairment (RI) in a general type 2 diabetes (T2D) population. METHODS We included 94 446 patients with T2D (56% men, age 68.3±11.6 years, BMI 29.6±5.3 kg/m², diabetes duration 8.5±7.1 years; means±SD) with renal function (serum creatinine) reported to the Swedish National Diabetes Register (NDR) in 2009. RI was defined as estimated glomerular filtration (eGFR)<60 ml/min/1.73 m² and albuminuria as a urinary albumin excretion rate (AER) >20 μg/min. We linked the NDR to the Swedish Prescribed Drug Register, and the Swedish Cause of Death and the Hospital Discharge Register to evaluate ongoing medication and clinical outcomes. RESULTS 17% of the patients had RI, and 62% of these patients were normoalbuminuric. This group of patients had better metabolic control, lower BMI, lower systolic blood pressure and were more often women, non-smokers and more seldom had a history of cardiovascular disease as compared with patients with albuminuric RI. 28% of the patients with normoalbuminuric RI had no ongoing treatment with any RAAS-blocking agent. Retinopathy was most common in patients with RI and albuminuria (31%). CONCLUSIONS The majority of patients with type 2 diabetes and RI were normoalbuminuric despite the fact that 25% of these patients had no ongoing treatment with RAAS-blocking agents. Thus, RI in many patients with type 2 diabetes is likely to be caused by other factors than diabetic microvascular disease and ongoing RAAS-blockade.

Comparing changes in plasma and skin autofluorescence in low-flux versus high-flux hemodialysis

Background Tissue advanced glycation end products (AGE) are increased in hemodialysis (HD) patients, especially those with cardiovascular complications. Skin autofluorescence (skin-AF) can noninvasively estimate the accumulation of AGE in tissue. The aim was to clarify whether HD using a high-flux (HF) dialyzer favors plasma- or skin-AF removal compared to low-flux (LF) dialysis. Material and methods 28 patients were treated with either an HF-HD or LF-HD but otherwise unchanged conditions in a cross-over design. A glucose containing dialysate was used. Skin-AF was measured noninvasively with an AGE reader before and after HD. Fluorescence (370 nm/465 nm) of plasma (p-AF) was determined as total and nonprotein-bound fractions. Correction for hemoconcentrations were made using the change in serum albumin. Paired and nonpaired statistical analyses were used. Results Skin-AF was unchanged after LF- and HF-dialysis. Total, free, and protein- bound p-AF was reduced after a single LF-HD by 21%, 28%, and 17%, respectively (P<.001). After HF HD total and free p-AF was reduced by 5% and 15%, respectively (P<.001), while protein bound values were unchanged. The LF-HD resulted in a more pronounced reduction of p-AF than did HF HD (P<.001). Serum albumin correlated inversely with p-AF in HF-HD. Conclusions In the dialysis settings used there was no significant change in skin AF after dialysis, with LF or with HF dialysis. Although only limited reduction in plasma fluorescence was observed, this was more pronounced when performing LF dialysis. These data are not in overwhelming support of the use of HF dialysis in the setting used in this study.

Dimensions of Arteriovenous Fistulas in Patients with Autosomal Dominant Polycystic Kidney Disease

Background/Aim: Aneurysms are known manifestations of autosomal dominant polycystic kidney disease (ADPKD). We investigated whether the dimensions of arteriovenous fistulas created for performance of haemodialysis were affected by the original disease. Methods: The lumen diameter of the fistula was studied by ultrasound in 19 patients with ADPKD and in 19 control patients. The patients’ sex, age, the duration of their fistulas, haemoglobin values and blood pressure levels were similar in both groups. The monitoring was performed along the forearm part of the vein, and the maximal diameter was measured. The diameters at the two needle insertion sites were also measured. Results: The ADPKD patients had a significantly higher fistula diameter than the control patients: 12 (range 8–19) mm versus 8 (range 6–24) mm at the widest level (p = 0.003). There were no significant differences in the diameters at the needle insertion sites. Conclusion: The receiving veins of arteriovenous fistulas in patients with ADPKD have an abnormality that causes a greater than normal dilatation in response to the arterialization. We postulate that this phenomenon is linked with the increased prevalence of aneurysms in ADPKD.

Echocardiographic findings in kidney transplant patients with autosomal dominant polycystic kidney disease

Objective. Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder with a tendency for aneurysm formation which may also affect the heart. ADPKD kidney transplant patients were studied by echocardiography. Material and methods. The case–control study consisted of 21 kidney transplant recipients and a group of 21 transplant patients with other diagnoses. They were in a stable phase a median of 3 years (range 1–10) after transplantation. M-mode and two-dimensional echocardiography were performed. Results. Age, haemoglobin and renal function were not different between the groups but ADPKD patients had significantly lower systolic blood pressure (p=0.004). There were no abnormalities in the aortic or mitral valve in either group. The diameter of the left ventricular outflow tract, the bulb or the ascending aorta did not differ between the groups. The diameters of the left ventricle or atrium were also similar. The left ventricular mass index was 132±36 in ADPKD patients versus 163±63 g/m2 in the controls (p=0.11). The left ventricular ejection fraction was 69±9.0 versus 70±8.9%. Early and atrial filling waves were equal. Conclusion. Valvular anomalies were infrequent. Aneurysm formation in the aorta and signs of dilated cardiomyopathy were not increased in patients with ADPKD.

A fixed protocol for outpatient clinic routines in the care of patients with severe renal failure.

Abstract Background: The primary aim of this study was to assess whether a fixed protocol, using a specially trained team, for intermediate follow-up to fulfillment of guideline targets is non-inferior to conventional follow-up in the care of uraemic patients. A secondary aim was to investigate possible impact on patient outcome. Methods: The cohort comprised 424 patients from seven centers. Inclusion criteria were either serum creatinine exceeding 200 µmol/l or calculated clearance below 30 ml/min, representing CKD 4 or 5a. Six centers followed a standardized protocol (group 1). One center provided controls (group 2). The study design was prospective and interventional. The variables measured were blood hemoglobin, bicarbonate, calcium, phosphate, intact parathyroid hormone, albumin, renal function variables, blood pressure and RAAS blockade. The number of patients achieving the set goals was analyzed as a time trend to determine if the intervention resulted in an improvement. Results: At baseline, group 1 had significantly lower GFR and higher serum creatinine, calcium, phosphate, calcium × phosphate product and bicarbonate, lower mean arterial pressure (MAP), systolic blood pressures and less use of RAAS. During the intervention, group 1 improved in the direction of guidelines for blood hemoglobin, albumin, bicarbonate and MAP. Outcome of secondary endpoints gave a risk of death of 30% in both groups, while the risk of renal replacement therapy was higher in group 1. Conclusions: However, the time to renal replacement therapy was significantly shorter in the intervention group, indicating that other variables than guideline achievements are important for the patient.