Blood Pressure Treatment in Kidney Transplant Recipients-Can We Improve?

Hypertension in kidney transplant (KTx) recipients is common, affecting both patient and graft survival. Annual data from the Norwegian Renal Registry reveal that <50% of adult (>18 y) KTx recipients reach target blood pressure (BP) ≤130/80 mm Hg. The aim of this study was to identify the determinants of failure to achieve BP control. METHODS: In conjunction with the 2018 annual data reporting, additional questions were added for recipients with BP >130/80 mm Hg (treating physician´s target BP for each patient, reasons for not achieving target, method of measurement). RESULTS: Annual forms were received from 98% (3407 of 3486) of KTx recipients, with 1787 (52%) reporting a BP >130/80 mm Hg ("above-target" group). These recipients were older, mostly male, with higher body mass index and serum creatinine levels (P < 0.05) compared with patients with controlled hypertension ("on-target" group). Valid survey answers were available for 84% of the "above-target" group (Survresp) with no significant demographic differences versus nonresponders (Survnonresp). Among Survresp, 32% were under antihypertensive dose titration, whereas dose-limiting side effects were reported in 7%. Target BP was confirmed to 130/80 mm Hg for 60% of Survresp. In recipients for whom the treating physician set target BP >130/80 mm Hg, 51% did not reach these individual targets. The number of antihypertensive drugs was significantly higher in the "above-target" group versus "on-target" group (mean 2.1 ± 1.2 versus 1.8 ± 1.3) and 36% versus 25% used ≥3 antihypertensive drugs (P < 0.05). Automatic attended BP measurement was utilized by 51%. CONCLUSIONS: In KTx recipients, a higher BP target achievement seems possible, potentially in the range of 75%-80%.

Clinical Phenotypes and Long-term Prognosis in White Patients With Biopsy-Verified Hypertensive Nephrosclerosis.

INTRODUCTION: Hypertensive nephrosclerosis is considered the second most common cause of end-stage renal disease (ESRD), but it is still an insufficiently studied and controversial disease entity. More information on the phenotype and prognosis is needed to improve clinical diagnostics and treatment. METHODS: We included all Norwegian patients with chronic kidney disease (CKD) referred for kidney biopsy between 1988 and 2012 whose clinical presentation was consistent with, but not primarily suspicious for, hypertensive nephrosclerosis (n = 4920); follow-up continued until 2013. RESULTS: A total of 918 patients (19%) had biopsy-verified hypertensive nephrosclerosis (i.e., arterionephrosclerosis). Their most common biopsy indications were proteinuria (57%), low estimated glomerular filtration rate (eGFR) (44%), hematuria (34%), or combinations of these indications. Multivariable logistic regression analysis revealed that arterionephrosclerosis was significantly associated with higher age, male sex, not having diabetes, higher blood pressure, lower proteinuria, and not having hematuria (P < 0.01 for all). Body mass index, cholesterol, high-density lipoprotein cholesterol, and eGFR were not significantly associated with arterionephrosclerosis (P > 0.05 for all). The most common biopsy-verified diagnoses in patients fulfilling the clinical criteria for hypertensive nephrosclerosis were arterionephrosclerosis (40%), glomerulonephritis (22%), and interstitial nephritis (14%), reflecting that the criteria had low sensitivity (0.17) and high specificity (0.94). ESRD and mortality risks did not differ in patients with arterionephrosclerosis compared to patients with glomerulonephritis, interstitial nephritis, or other relevant diagnoses (P > 0.1 for both), whereas patients with diabetic kidney disease had a 2-fold higher risk (P < 0.001 for both). CONCLUSION: Arterionephrosclerosis is a high-risk disease, often with an atypical phenotype with proteinuria and hematuria contributing to low accuracy for current clinical criteria for hypertensive nephrosclerosis.

Proteinase-3 and myeloperoxidase serotype in relation to demographic factors and geographic distribution in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

Background: In anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, antigen specificity varies between myeloperoxidase (MPO) and proteinase 3 (PR3). This has been reported to vary in relation to age, gender, geography and extrarenal manifestations. However, studies are difficult to compare as criteria for inclusion vary. The aim of this study was to investigate the relationship between ANCA serotype, latitude, ultraviolet (UV) radiation levels, age, gender and renal function at diagnosis in a large study with uniform inclusion criteria. Methods: Patients with biopsy-proven ANCA-associated glomerulonephritis were identified from regional or nationwide registries in 14 centres in Norway, Sweden, the UK, the Czech Republic, Croatia, Italy and the USA during the period 2000-13. UV radiation levels for 2000-13 in Europe were obtained from the Swedish Meteorological and Hydrological Institute. Results: A total of 1408 patients (45.2% PR3-ANCA) were included in the study. In univariable analysis, PR3-ANCA was significantly associated with male gender {odds ratio [OR] 2.12 [95% confidence interval (CI) 1.71-2.62]}, younger age [OR per year 0.97 (95% CI 0.96-0.98)] and higher glomerular filtration rate [OR per mL/min 1.01 (95% CI 1.01-1.02); P < 0.001] at diagnosis but not with latitude or UV radiation. In multivariable logistic regression analysis, latitude and UV radiation also became significant, with higher odds for PR3-ANCA positivity at northern latitudes/lower UV radiation levels. However, the latitudinal difference in MPO:PR3 ratio is smaller than differences previously reported concerning microscopic polyangiitis and granulomatosis with polyangiitis. Conclusions: The ratio between PR3-ANCA and MPO-ANCA varies in glomerulonephritis with respect to age, gender, renal function and geographic latitude/UV radiation levels.

Reference limits for chromogranin A, CYFRA 21-1, CA 125, CA 19-9 and carcinoembryonic antigen in patients with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) may have increased plasma concentrations of some tumor markers even when no cancer is present. Previous studies have indicated that plasma concentrations of chromogranin A (CGA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) are higher in patients with CKD but without cancer, than in healthy individuals, and this can make interpretation of results more complicated. The aim of this study was to establish reference limits for these markers in patients with CKD not receiving dialysis and with no clinical evidence of cancer. METHODS: We measured plasma concentrations in samples from 131 patients with CKD due to various etiologies and studied the association of tumor marker concentrations with estimated glomerular filtration rate (GFR) and other patient characteristics. RESULTS: Estimated reference limits for plasma CA 125, CA 19-9 and CEA were approximately the same as for healthy populations. Serum concentrations of CGA and CYFRA 21-1 correlated strongly with estimated GFR, and GFR-dependent reference limits were estimated. CONCLUSIONS: GFR-dependent reference limits for CGA and CYFRA 21-1 are reported in order to support interpretation of these markers in patients with CKD.

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.

Characteristics and Outcomes of Granulomatosis With Polyangiitis (Wegener) and Microscopic Polyangiitis Requiring Renal Replacement Therapy: Results From the European Renal Association-European Dialysis and Transplant Association Registry.

BACKGROUND: This study describes the incidence and outcomes of European patients requiring renal replacement therapy (RRT) for kidney failure due to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 12 renal registries providing individual RRT patient data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry in 1993-2012 participated. PREDICTOR: Cause of primary kidney disease: AAV (ie, granulomatosis with polyangiitis [Wegener] and microscopic polyangiitis) versus 3 separate matched control groups without AAV: (1) primary glomerulonephritis, (2) diabetes mellitus, and (3) disease other than diabetes mellitus as the cause of primary kidney disease, including glomerulonephritis (termed "nondiabetes"). OUTCOMES: Incidence, causes of death, and survival. MEASUREMENTS: ERA-EDTA primary renal disease codes. RESULTS: 2,511 patients with AAV (1,755, granulomatosis with polyangiitis; 756, microscopic polyangiitis) were identified, representing an incidence of 1.05 per million population (pmp) for granulomatosis with polyangiitis (predominating in Northern Europe) and 0.45 pmp for microscopic polyangiitis (prevailing in Southern Europe). Kidney transplantation was performed in 558 (22.2%) patients with vasculitis. The 10-year probability for survival on RRT after day 91 was 32.5% (95% CI, 29.9%-35.1%) in patients with vasculitis. Survival on RRT after day 91 did not differ between AAV and matched nondiabetes patients. Patient and transplant survival after kidney transplantation, adjusted for time period and country, was better in AAV than in matched nondiabetes patients (HRs of 0.81 [95% CI, 0.67-0.99] and 0.82 [95% CI, 0.69-0.96], respectively). LIMITATIONS: No data for extrarenal manifestations, treatment, and relapses. CONCLUSIONS: Geographical differences in the incidence of RRT for kidney failure due to granulomatosis with polyangiitis and microscopic polyangiitis copied their distribution in the general population. Overall survival on RRT after day 91 for patients with AAV was similar to that for patients with nondiabetes diagnoses. Our results suggest that patients with AAV are suitable candidates for kidney transplantation with favorable survival outcomes.

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.

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 m(2)) 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.

[The use of diuretics in kidney disease]. / Bruk av diuretika ved nyresykdom.

BACKGROUND: Diuretics are an important part of the therapy for a number of medical conditions such as heart, liver and kidney failure and hypertension. This article presents updated knowledge on the use of diuretics in kidney disease. METHOD: The article is based on a literature search in PubMed, information obtained from textbooks on neurophysiology and kidney disease and on the authors' clinical experience. RESULTS: Kidney disease affects the pharmacokinetics and pharmacodynamics of diuretics, and this must be taken into account when selecting a drug and determining the dosage. This applies particularly to nephrotic syndrome and severe chronic renal disease (GFR < 30 ml/min/1.73 m²). INTERPRETATION: Knowledge of the pharmacology of diuretics is crucial to the rational use of diuretics in renal disease. Dose titration under close clinical monitoring and an optimal dosage interval make it possible to find the lowest possible effective dose and reduce the occurrence of side effects.

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

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.

Nutritional problems, overhydration and the association with quality of life in elderly dialysis patients.

PURPOSE: The aim of this pilot study was to describe the hydration and nutritional status of a cohort of elderly dialysis patients and to explore the association between these parameters and the quality of life (QoL). METHODS: All patients over 75 years of age being in chronic dialysis by January 2008 at 3 dialysis units (n=34) were asked to participate in this pilot study, 24 patients were entered. Hydration status was assessed by bioimpedance spectroscopy (BIS) and nutritional status by the subjective global assessment (SGA), BIS, anthropometric measures and biochemical parameters. Based on these assessments the patients were classified as being cachectic or not according to newly defined criteria. QoL was measured using the SF-36. RESULTS: The results showed cachexia in 6 (25%), 37.5% had a body mass index below 24, whereas according to SGA 91% were malnourished. BIS showed low lean tissue index in 46% and overhydration in 35% of the patients. Compared to non-cachectic and normohydrated, cachectic and overhydrated patients reported consistently poorer QoL. For cachectic patients, the differences were clinically significant for all SF-36. BIS was easily applicable when used before dialysis. CONCLUSIONS: The high frequency of nutritional deficits in this study calls for more attention to nutritional status in elderly dialysis patients. There is a need for a general agreement on how nutritional status should be assessed and reported, both in clinics and in research.

End-stage renal disease and recruitment to randomized trials: why is it so difficult? Results from a survey among Norwegian nephrologists.

OBJECTIVE: Recruitment is one of the most serious challenges in randomized clinical trials (RCTs), especially in the old and frail population. A Norwegian multicentre RCT targeting end-stage renal disease (ESRD) patients older than 70 years was initiated to compare the impact on quality of life of early or late start of dialysis. Owing to poor inclusion the RCT was closed. The aim of the present study was to explore possible reasons for the recruitment failure. MATERIAL AND METHODS: A questionnaire was distributed to all Norwegian nephrologists. The questionnaire presented 11 statements which cited possible reasons for not including elderly ESRD patients in the RCT in question. RESULTS: The highest rated reasons for non-inclusion were the physician's wish to decide the timing of dialysis individually and the patient's wish to postpone the start of treatment. High mean scores were also found for reasons related to workload and capacity at the dialysis unit, whereas the influence of the doctor-patient relationship and competing studies were judged not to be important. CONCLUSIONS: The results indicate that confidence in individually decided treatment and fear of losing professional autonomy make Norwegian nephrologists reluctant to include patients in RCTs. To succeed in recruitment, there seems to be a need for cultural changes as well as increased resources to meet practical challenges.

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.

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 >or=18 years and duration of dialysis >or=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 >or= 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.

Association of kidney function and albuminuria with cardiovascular mortality in older vs younger individuals: The HUNT II Study.

BACKGROUND: The cardiovascular risk implications of a combined assessment of reduced kidney function and microalbuminuria are unknown. In elderly persons, traditional cardiovascular risk factors are less predictive, and measures of end organ damage, such as kidney disease, may be needed for improved cardiovascular mortality risk stratification. METHODS: The glomerular filtration rate was estimated from calibrated serum creatinine, and the urine albumin-creatinine ratio (ACR) was measured in 3 urine samples in 9,709 participants of the second Nord-Trøndelag Health Study (HUNT II), a Norwegian community-based health study, followed for 8.3 years with a 71% participation rate. RESULTS: An estimated glomerular filtration rate (EGFR) at levels of less than 75 mL/min/1.73 m(2) was associated with higher cardiovascular mortality risk, whereas a higher ACR was associated with higher risk with no lower limit. Low EGFR and albuminuria were synergistic cardiovascular mortality risk factors. Compared with subjects with an EGFR greater than 75 mL/min/1.73 m(2) and ACR below the sex-specific median who were at the lowest risk, subjects with an EGFR of less than 45 mL/min/1.73 m(2) and microalbuminuria had an adjusted incidence rate ratio of 6.7 (95% confidence interval, 3.0-15.1; P < .001). The addition of ACR and EGFR improved traditional risk models: 39% of subjects with intermediate risk were reclassified to low- or high-risk categories with corresponding observed risks that were 3-fold different than the original category. Age-stratified analyses showed that EGFR and ACR were particularly strong risk factors for persons 70 years or older. CONCLUSIONS: Reduced kidney function and microalbuminuria are risk factors for cardiovascular death, independent of each other and traditional risk factors. The combined variable improved cardiovascular risk stratification at all age levels, but particularly in elderly persons where the predictive power of traditional risk factors is attenuated.

Long-term risk of cancer in membranous nephropathy patients.

BACKGROUND: There is a well-known association between membranous nephropathy (MN) and cancer, and patients with MN usually are examined for cancer at the time of diagnosis. The long-term risk of cancer after MN is not well studied. STUDY DESIGN: Cohort study with record linkage between the Norwegian Kidney Biopsy Registry and Norwegian Cancer Registry. SETTING & PARTICIPANTS: 161 patients with MN from 1988 to 2003. PREDICTOR: Patients with MN compared with the age- and sex-adjusted general Norwegian population. OUTCOMES: Cancer diagnosis reported through 2003. RESULTS: Mean duration of follow-up was 6.2 years (range, 0.1 to 15 years). 33 patients developed cancer; including 24 patients with cancer after the diagnosis of MN. Median time from diagnosis of MN to diagnosis of cancer was 60 months (range, 0 to 157 months). Mean annual incidence ratio of cancer was 2.4/100 person-years (2.1/100 person-years in the 0- to 5-year period and 2.8/100 person-years for the 5 to 15 years after kidney biopsy). During the 0 to 15 years after the diagnosis of MN, the expected number of cancers was 10.7, resulting in a standardized incidence ratio of cancer of 2.25 (95% confidence interval, 1.44 to 3.35). In the 5 to 15 years after diagnosis, standardized incidence ratio was 2.30 (95% confidence interval, 1.19 to 4.02). Patients with MN who developed cancer were older (65 versus 52 years; P < 0.001). Patients with cancer and MN had a greater mortality rate than patients without cancer (67% versus 26%; P < 0.001). LIMITATIONS: Follow-up treatment after MN with cytotoxic and immunosuppressive medications is not known. CONCLUSIONS: An increased risk of developing cancer is observed after the diagnosis of MN, which persists for many years.

[Systemic lupus erythematosus and pregnancy]. / Systemisk lupus erythematosus og svangerskap.

BACKGROUND: Systemic lupus erythematosus (SLE) often starts in women of fertile age. Due to the unpredictable nature of the disease and the increased risk of the disease flaring up during pregnancy, women with SLE have previously often been advised to avoid pregnancy. This summary reviews current insights in pregnancy management of women with SLE. METHOD: Search in the Medline database (period 1980-2005) using keywords: SLE, lupus nephritis, antiphospholipid antibody, neonatal lupus and pregnancy. RESULTS: Previous studies of pregnant women with SLE have had different designs, sample sizes, selections of patients, definitions and measures of outcome. Women with previous pregnancy losses, an ongoing active disease with nephritis or hypertension and positive antiphospholipid antibodies, have an increased risk of pregnancy loss. The most favourable pregnancy outcomes are achieved when conception takes place during a remission of the disease. INTERPRETATION: There are few absolute contraindications for pregnancies in women with SLE. Women with SLE may experience uncomplicated pregnancies, but they need to plan their pregnancies as the risk for complications is increased. Best results are achieved through the cooperation of rheumatologists, gynaecologists and nephrologists. Glucocorticosteroids, hydroxychlorocine, azathioprine and anticoagulation may be used during pregnancy.