Knut Aasarød

Abdominal aortic calcification in dialysis patients: results of the CORD study

Background. Patients with chronic kidney disease stage 5 have a high prevalence of vascular calcification, but the specific anatomical distribution and severity of abdominal aortic calcification (AAC), in contrast to coronary calcification, is less well documented. AAC may be recorded using plain radiographs. The present report is an analysis of baseline data on AAC in patients enrolled in the CORD (Calcification Outcome in Renal Disease) study. Methods. A total of 47 centres in six European countries participated in this cross-sectional study. Inclusion criteria were age ≥18 years and duration of dialysis ≥3 months. Lateral lumbar radiography of the abdominal aorta was used to determine the overall AAC score, which is related to the severity of calcific deposits at lumbar vertebral segments L1–L4. The reliability of the method was tested by double reading of 64 radiographs (coefficient of correlation 0.9). Results. A lateral lumbar radiograph was obtained in 933 patients. Calcification (AAC score ≥ 1) was present in 81% of the patients; its severity increased significantly from L1 to L4 (P < 0.0001) and affected all of these segments in 51% of patients. Independent predictors for the presence and severity of calcification were age (odds ratio [OR] 1.103/year; P < 0.0001), duration of dialysis (OR 1.110/year; P = 0.002) and history of cardiovascular disease (OR 3.247; P < 0.0001). Conclusions. AAC detected by lateral lumbar radiograph is associated with several risk factors of uraemic calcification. This semi-quantitative method is more widely available and less expensive than the current procedures for studying calcification and could form part of a pre-transplant workup and cardiovascular risk stratification.

Trends in dialysis modality choice and related patient survival in the ERA-EDTA Registry over a 20-year period.

BACKGROUND Although previous studies suggest similar patient survival for peritoneal dialysis (PD) and haemodialysis (HD), PD use has decreased worldwide. We aimed to study trends in the choice of first dialysis modality and relate these to variation in patient and technique survival and kidney transplant rates in Europe over the last 20 years. METHODS We used data from 196 076 patients within the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry who started renal replacement therapy (RRT) between 1993 and 2012. Trends in the incidence rate and prevalence on Day 91 after commencing RRT were quantified with Joinpoint regression. Crude and adjusted hazard ratios (HRs) for 5-year dialysis patient and technique survival were calculated using Cox regression. Analyses were repeated using propensity score matching to control for confounding by indication. RESULTS PD prevalence dropped since 2007 and HD prevalence stabilized since 2009. Incidence rates of PD and HD decreased from 2000 and 2009, respectively, while the incidence of kidney transplantation increased from 1993 onwards. Similar 5-year patient survival for PD versus HD patients was found in 1993-97 [adjusted HR: 1.02, 95% confidence interval (95% CI): 0.98-1.06], while survival was higher for PD patients in 2003-07 (HR: 0.91, 95% CI: 0.88-0.95). Both PD (HR: 0.95, 95% CI: 0.91-1.00) and HD technique survival (HR: 0.93, 95% CI: 0.87-0.99) improved in 2003-07 compared with 1993-97. CONCLUSIONS Although initiating RRT on PD was associated with favourable patient survival when compared with starting on HD treatment, PD was often not selected as initial dialysis modality. Over time, we observed a significant decline in PD use and a stabilization in HD use. These observations were explained by the lower incidence rate of PD and HD and the increase in pre-emptive transplantation.

Clinical Outcome of Patients with Wegener’s Granulomatosis Treated with Plasma Exchange

We report the clinical course of 29 patients with Wegener’s granulomatosis (WG) treated with plasma exchange (PE) in Norway in the period from 1988 to 1999. Median follow-up was 41.5 months. The mean number of exchanges was 8.5 ± 5.8 (range 2–32). Median serum creatinine concentration was 400 µmol/l (range 90–1,356) and 17 patients were dialysis dependent at presentation. Two- and five-year patient survival was 75 and 71%, respectively, and renal (ESRD-free) survival was 74 and 54%, respectively. Seven (50%) of the 14 patients alive in the dialysis group had discontinued dialysis within the first month, and 6 (50%) of 12 patients alive at follow-up had independent renal function. No patients, however, had normal serum creatinine concentration. Median time until development of ESRD for patients presenting with a need for dialysis was ∼32 months. The development of ESRD in 79 patients treated with immunosuppression alone was significantly lower, but when adjusted for serum creatinine there was no difference between patients treated with or without PE. Although a considerable fraction of patients with WG and severe renal involvement regain independent renal function, few will have normal serum creatinine concentration at follow-up, despite the addition of PE as adjunctive therapy.

Wegener's granulomatosis: Inflammatory cells and markers of repair and fibrosis in renal biopsies: A clinicopathological study

Objective: This study aimed to quantitate inflammatory cells in renal biopsies from patients with Wegeners granulomatosis (WG) and to identify cells participating in early fibrogenesis. The goal was to determine whether these cells correlated with the severity of renal disease and whether their presence had a bearing on renal prognosis. Material and Methods: Sixty-one patients with WG who had a renal biopsy taken at the time of diagnosis were included in the study. Immunostaining with monoclonal antibodies towards macrophages (CD68), T- and B-lymphocytes, f -smooth muscle actin ( f -SMA) and vimentin was done. Results: The dominating intraglomerular leucocytes were macrophages (29.9 - 15 cells/glomerular cross-section) and to a lesser extent T-cells (2.57 - 1.8 cells/glomerular cross-section). No B-lymphocytes were detected in the glomeruli. More than two-thirds of the T-cells were CD8 + (cytotoxic) cells. Macrophages and T-lymphocytes were distributed equally in the renal interstitium and were numerous around crescentic glomeruli. Glomerular and interstitial macrophages and interstitial T-cells correlated significantly with serum (S-) creatinine at the time of biopsy but not after 1 year. S-creatinine at the time of biopsy and after 1 year differed significantly among the three levels of interstitial f -SMA staining. S-creatinine at biopsy was highest when tubular vimentin staining was strongest, and tubular vimentin staining was strongest in patients with acute tubular damage. Conclusions: Evidence was found for a cellular type IV immune response in WG, with CD8 + T-lymphocytes and macrophages dominating the cellular infiltrate. The detection of interstitial f -SMA, probably staining myofibroblasts implicated in renal fibrogenesis, indicated a low glomerular filtration rate 1 year after renal biopsy.OBJECTIVE This study aimed to quantitate inflammatory cells in renal biopsies from patients with Wegeners granulomatosis (WG) and to identify cells participating in early fibrogenesis. The goal was to determine whether these cells correlated with the severity of renal disease and whether their presence had a bearing on renal prognosis. MATERIAL AND METHODS Sixty-one patients with WG who had a renal biopsy taken at the time of diagnosis were included in the study. Immunostaining with monoclonal antibodies towards macrophages (CD68), T- and B-lymphocytes, alpha-smooth muscle actin (alpha-SMA) and vimentin was done. RESULTS The dominating intraglomerular leucocytes were macrophages (29.9 +/- 15 cells/glomerular cross-section) and to a lesser extent T-cells (2.57 +/- 1.8 cells/glomerular cross-section). No B-lymphocytes were detected in the glomeruli. More than two-thirds of the T-cells were CD8+ (cytotoxic) cells. Macrophages and T-lymphocytes were distributed equally in the renal interstitium and were numerous around crescentic glomeruli. Glomerular and interstitial macrophages and interstitial T-cells correlated significantly with serum (S-) creatinine at the time of biopsy but not after 1 year. S-creatinine at the time of biopsy and after 1 year differed significantly among the three levels of interstitial alpha-SMA staining. S-creatinine at biopsy was highest when tubular vimentin staining was strongest, and tubular vimentin staining was strongest in patients with acute tubular damage. CONCLUSIONS Evidence was found for a cellular type IV immune response in WG, with CD8+ T-lymphocytes and macrophages dominating the cellular infiltrate. The detection of interstitial alpha-SMA, probably staining myofibroblasts implicated in renal fibrogenesis, indicated a low glomerular filtration rate 1 year after renal biopsy.

Improved prognosis in Norwegian patients with glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies

Background Glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased mortality and a high risk of end-stage renal disease (ESRD). Here, we investigated whether the prognosis has improved over the last 25 years. Methods Patients were identified in the Norwegian Kidney Biopsy Registry. We included all patients with pauci-immune crescentic glomerulonephritis and a positive ANCA test from 1988 to 2012. Deaths and ESRD in the cohort were identified through record linkage with the Norwegian Population Registry (deaths) and the Norwegian Renal Registry (ESRD). Outcomes of patients diagnosed in 1988–2002 were compared with outcomes of patients diagnosed in 2003–12. Results A cohort of 455 patients with ANCA-associated glomerulonephritis was identified. The mean follow-up was 6.0 years (range, 0.0–23.4). During the study period, 165 (36%) patients died and 124 (27%) progressed to ESRD. Compared with patients diagnosed in 1988–2002, those diagnosed in 2003–12 had higher mean initial estimated glomerular filtration rates (37 versus 27 mL/min/1.73 m2) and lower risk of ESRD (1-year risk: 13 versus 19%; 10-year risk: 26 versus 37%). The composite endpoint, ESRD or death within 0–1 year after diagnosis, was reduced from 34 to 25%. In patients over 60 years old, 1-year mortality fell from 33 to 20%. Conclusions In Norwegian patients with ANCA-associated glomerulonephritis, prognosis was significantly better in 2003–12 compared with 1988–2002. This improvement was probably partly due to a shorter diagnostic delay, and better therapeutic management in older patients.

Arginine/asymmetric dimethylarginine ratio and cardiovascular risk factors in patients with predialytic chronic kidney disease

OBJECTIVES Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) that accumulates in patients with chronic kidney disease (CKD) and predicts cardiovascular outcome. Arginine is the substrate for NOS and a low arginine/ADMA ratio may lead to a reduced NO production and a worse prognosis. We have studied how other important CKD variables predict the arginine/ADMA ratio. DESIGN AND METHODS The population is 160 predialytic CKD patients (median age 61 years). We used backward stepwise regression to identify the best predictors of p-arginine, p-ADMA and arginine/ADMA ratio. RESULTS P-ADMA was predicted by estimated GFR (eGFR) (adjusted R(2)=0.17, p>0.00). Arginine/ADMA ratio was predicted by gender, eGFR, use of renin angiotensin aldosteron (RAAS) inhibitors, current smoking and use of platelet inhibitors (adjusted R(2)=0.18, p<0.00). CONCLUSIONS Reduced eGFR is associated with reduced arginine/ADMA ratio. The use of RAAS inhibitors and male gender may be protective against a low arginine/ADMA ratio.

Outcome in biopsy-proven Lupus nephritis: Evaluation of biopsies from the Norwegian Kidney Biopsy Registry:

Objective To evaluate long-term mortality and end-stage renal disease (ESRD) in a cohort of Norwegian patients with biopsy-proven lupus nephritis (LN). Methods Renal biopsies were obtained from 178 patients with LN from 1988 until 2007. Mortality rate and death causes were provided by Statistics Norway and ESRD data were provided by the Norwegian Renal Registry. Risk factors for all-cause mortality were evaluated by Cox regression. Standardized mortality ratio (SMR) was compared to observed deaths in a matched general population sample. Results Mean age was 37.6 (±14.4) years, and median time of follow-up was 8.5 years (0–26.2). Thirty-six patients (20.2%) died during follow-up. The SMR for all-cause mortality was 5.6 (Confidence interval [CI] 3.7–7.5). In an adjusted multivariate analysis proliferative glomerulonephritis (LN class IV) was independently associated with all-cause mortality; hazard ratio (HR) 2.6 (Confidence interval [CI] 1.2–5.7 p = 0.017). Main causes of death were infections (47.2%) and cardiovascular events 8 (22.2%). Thirty-six patients (20.2%) reached ESRD. Conclusions Biopsy-proven LN is associated with increased mortality compared to the general population. LN class IV is associated with all-cause mortality. Infections and cardiovascular events were the most common causes of death. Patients with LN have a high incidence of ESRD.

The impact of nutritional status, physical function, comorbidity and early versus late start in dialysis on quality of life in older dialysis patients

Abstract Background: For the majority of the older patients in dialysis, the treatment will be lifelong. Thus, quality of life (QoL) is a crucial outcome. Our aim was to assess the QoL of older Norwegian dialysis patients and to investigate the impact of early (estimated glomerular filtration rate, eGFR ≥10 mL/min) versus late (eGFR <10 mL/min) start in dialysis, comorbidity, nutritional status and physical capacity. Methods: A self-report questionnaire including SF-36 (QoL) and the Subjective Global Assessment (SGA; nutritional status) was mailed to all patients (n = 320) ≥75 years registered in the Norwegian Renal Registry (NRR) as being in dialysis by September 2009. Reply was received from 233 patients (73%). Medical data including comorbidities and eGFR at dialysis start (obtained for 194 patients) were retrieved from the NRR. Functional capacity was determined from the SGA. Results: Compared to reports from younger dialysis patients, our patients scored poorer on all SF-36 subscales. Early start in dialysis was registered for 52 patients, 142 patients started late, 51.4% were well nourished (SGA A), 32.3% moderately malnourished (SGA B) and 16.4% were severely malnourished (SGA C). No significant association between any SF-36 scores and early versus late start, nutritional status or comorbidity was found. Better physical function was significantly associated with better scores on all SF-36 scales. Conclusions: Our results indicate that physical function is important to all QoL aspects. Increased focus on physical rehabilitation seems pertinent. Early start of dialysis treatment was not associated with better long term QoL scores.

Arginine, dimethylated arginine and homoarginine in relation to cardiovascular risk in patients with moderate chronic kidney disease

OBJECTIVES Arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine/ADMA ratio and homoarginine could potentially affect nitric oxide production and have been studied in relation to cardiovascular risk (CVR) in various clinical populations. Prospective studies on the CVR associated with arginine/ADMA ratio and homoarginine in patients with moderate chronic kidney disease (CKD) are still scarce. We have studied how arginine, homoarginine and dimethylated arginine can predict cardiovascular events in such a population. DESIGN AND METHODS We measured plasma concentrations of arginine (P-arginine), ADMA (P-ADMA), SDMA (P-SDMA), homoarginine (P-homoarginine) and other covariates in 160 patients with predialytic CKD (mean age 57 years and mean eGFR 43 mL/min/1.73 m(2)) and followed them for 58 months in median. The risks of fatal and non-fatal cardiovascular events associated with the predictors were evaluated with multivariable Cox proportional hazard analysis. RESULTS There were 31 cardiovascular events during the observation period. In a multivariable model adjusted for age, sex, previous cardiovascular disease, P-cystatin C and P-homoarginine, the hazard ratio (HR) associated with an increase in arginine/ADMA ratio by 10 was 0.83 (P=0.03). The HR of a 1 μmol/L increase in P-homoarginine in the same model was 1.78 (P=0.01). A statistically significant interaction between P-homoarginine and P-cystatin C was found in an extended multivariable model. P-SDMA was not associated with increased CVR after adjustment for basic covariates. CONCLUSION This study demonstrates a negative association between arginine/ADMA ratio and CVR in CKD patients and a positive association between P-homoarginine and CVR. The latter is in contrast to what has been demonstrated by others.

A man in his 30s with recurrent vomiting and abdominal pain relieved by hot showers

A man in his 30s was admitted to the medical ward with nausea, retching, vomiting and abdominal pain. Seven years previously he had been admitted with stabbing retrosternal pain that worsened with intake of food and drink. At that time a small hiatus hernia of 1 – 2 cm and a small protrusion down towards the Z line were demonstrated. Over the following years the patient was admitted several times with corresponding symptoms. During the last admission it appeared that he smoked marijuana once a week. On examination on admission the patient had epigastric pain, he was sweating, felt nauseated and vomited green fluid. He had a lean stature. His blood pressure was 140/ 90 mm Hg, pulse 48 and the temperature measured in his ear was 35.4 °C. There was slight tenderness on light palpation in the epigastrium. There was no diarrhoea, he had had a normal bowel movement the same morning. His medication was pantoprazole 40 mg  1. He had smoked marijuana on the day before admission. Pantoprazole infusion was started. He had metabolic acidosis with base excess (BE) – 9.0 mmol/l (–3 – 3 mmol/l) and lactate 5.1 mmol/l (0.5 – 2.2 mmol/l) but the circulation was not affected. Blood tests showed a haemoglobin of 17.7 g/100 ml (13.4 – 17.0 g/100 ml), leukocytes 12.9  109/l (3.7 – 10.0  109/l), potassium 4.9 mmol/l (3.5 – 4.4 mmol/l) and glucose 8.4 mmol/l (4.2 – 6.3 mmol/l). The serum ethanol was negative.