Prior cancer and risk of monoclonal gammopathy of undetermined significance: a population-based study in Iceland and Sweden.

There is some evidence that a prior cancer is a risk factor for the development of multiple myeloma (MM). If this is true, prior cancer should be associated with a higher prevalence or increased progression rate of monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM and related disorders. Those with a history of cancer might therefore constitute a target population for MGUS screening. This two-part study is the first study to evaluate a relationship between MGUS and prior cancers. First, we evaluated whether prior cancers were associated with having MGUS at the time of screening in the Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) study that includes 75,422 individuals screened for MGUS. Next, we evaluated the association of prior cancer and the progression of MGUS to MM and related disorders in a population-based cohort of 13,790 Swedish individuals with MGUS. A history of prior cancer was associated with a modest increase in the risk of MGUS (odds ratio=1.10; 95% confidence interval: 1.00-1.20). This excess risk was limited to prior cancers in the year preceding MGUS screening. A history of prior cancer was associated with progression of MGUS, except for myeloid malignancies which were associated with a lower risk of progression (hazard ratio=0.37; 95% confidence interval: 0.16-0.89; P=0.028). Our findings indicate that a prior cancer is not a significant etiological factor in plasma cell disorders. The findings do not warrant MGUS screening or different management of MGUS in those with a prior cancer.

Validity of chronic disease diagnoses in Icelandic healthcare registries.

AIMS: To evaluate the validity of recorded chronic disease diagnoses in Icelandic healthcare registries. METHODS: Eight different chronic diseases from multiple sub-specialties of medicine were validated with respect to accuracy, but not to timeliness. For each disease, 30 patients with a recorded diagnosis and 30 patients without the same diagnosis were randomly selected from >80,000 participants in the iStopMM trial, which includes 54% of the Icelandic population born before 1976. Each case was validated by chart review by physicians using predefined criteria. RESULTS: The overall accuracy of the chronic disease diagnoses was 96% (95% CI 94-97%), ranging from 92 to 98% for individual diseases. After weighting for disease prevalence, the accuracy was estimated to be 98.5%. The overall positive predictive value (PPV) of chronic disease diagnosis was 93% (95% CI 89-96%) and the overall negative predictive value (NPV) was 99% (95% CI 96-100%). There were disease-specific differences in validity, most notably multiple sclerosis, where the PPV was 83%. Other disorders had PPVs between 93 and 97%. The NPV of most disorders was 100%, except for hypertension and heart failure, where it was 97 and 93%, respectively. Those who had the registered chronic disease had objective findings of disease in 96% of cases. CONCLUSIONS: When determining the presence of chronic disease, diagnosis data from the Icelandic healthcare registries has a high PPV, NPV and accuracy. Furthermore, most diagnoses can be confirmed by objective findings such as imaging or blood testing. These findings can inform the interpretation of studies using diagnostic data from the Icelandic healthcare registries.

Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study.

Serum free light chain (FLC) concentration is greatly affected by kidney function. Using a large prospective population-based cohort, we aimed to establish a reference interval for FLCs in persons with chronic kidney disease (CKD). A total of 75422 participants of the iStopMM study were screened with serum FLC, serum protein electrophoresis and immunofixation. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. Central 99% reference intervals were determined, and 95% confidence intervals calculated. Included were 6461 (12%) participants with measured FLCs, eGFR < 60 mL/min/1.73 m2, not receiving renal replacement therapy, and without evidence of monoclonality. Using current reference intervals, 60% and 21% had kappa and lambda FLC values outside the normal range. The FLC ratio was outside standard reference interval (0.26-1.65) in 9% of participants and outside current kidney reference interval (0.37-3.10) in 0.7%. New reference intervals for FLC and FLC ratio were established. New reference intervals for the FLC ratio were 0.46-2.62, 0.48-3.38, and 0.54-3.30 for eGFR 45-59, 30-44, and < 30 mL/min/1.73 m2 groups, respectively. The crude prevalence of LC-MGUS in CKD patients was 0.5%. We conclude that current reference intervals for FLC and FLC ratio are inaccurate in CKD patients and propose new eGFR based reference intervals to be implemented.

Mild Stage 1 post-operative acute kidney injury: association with chronic kidney disease and long-term survival.

BACKGROUND: Mild cases of acute kidney injury (AKI) are identified by a small rise in serum creatinine (SCr) according to the KDIGO AKI definition. The aim of this study was to examine the long-term outcomes of individuals with mild AKI.Methods. This was a retrospective cohort study of all adult patients who underwent abdominal, cardiothoracic, vascular or orthopaedic surgery at Landspitali-The National University Hospital of Iceland in 1998-2015. Incident chronic kidney disease (CKD), progression of pre-existing CKD and long-term survival were compared between patients with mild Stage 1 AKI (defined as a rise in SCr of ≥26.5 µmol/L within 48 h post-operatively without reaching 1.5× baseline SCr within 7 days), and a propensity score-matched control group without AKI stratified by the presence of CKD. RESULTS: Pre- and post-operative SCr values were available for 47 333 (42%) surgeries. Of those, 1161 (2.4%) had mild Stage 1 AKI and 2355 (5%) more severe forms of AKI. Mild Stage 1 AKI was associated with both incident CKD and progression of pre-existing CKD (P < 0.001). After exclusion of post-operative deaths within 30 days, mild Stage 1 AKI was not associated with worse 1-year survival in patients with preserved kidney function (94% versus 94%, P = 0.660), and same was true for patients with pre-operative CKD (83% versus 82%, P = 0.870) compared with their matched individuals. Conclusions. Mild Stage 1 AKI is associated with development and progression of CKD, but not with inferior 1-year survival. These findings support the inclusion of a small absolute increase in SCr in the definition of AKI.

[Epidemiology of acute kidney injury in a tertiary care university hospital according to the RIFLE criteria]. / Bradur nyrnaskadi a Landspitala 2008-2011 og ahaettupaettir og afdrif sjuklinga med alvarlegan skada.

INTRODUCTION: Acute kidney injury (AKI) is a common problem in hospitalized patients, requiring extensive treatment and carries a high mortality rate. This study was designed to assess the epidemiology of AKI, and risk factors and outcome of patients with severe AKI in a tertiary care university hospital in Iceland. MATERIAL AND METHODS: All adult patients with measured serum creatinine (SCr) in Landspitali University Hospital from January 2008 to December 2011, who had a measured baseline SCr in the preceeding six months, were included. Patients were categorized according to the RIFLE-criteria into risk (stage 1), injury (stage 2) and failure (stage 3) groups based on their highest SCr, using the lowest SCr in the previous six months as baseline. RESULTS: A total of 17,693 individuals (out of 74,960) had a baseline SCr and their data were used for analysis. AKI occurred in 3,686 (21%) with 12%, 5% and 4% of stage 1, 2 and 3, respectively. There were more females in stage 1 and stage 2 and more males in stage 3 (p< 0.001). Contributing causes for AKI in patients with stage 3 AKI were surgery (22%), circulatory shock (23%), sepsis (14%), cardiovascular insult (32%), respiratory failure (27%), bleeding (10%), trauma (7%) and AKI associated drugs (61%). Dialysis was required in 11% and in 0.7% for longer than 30 days but none > 90 days. One year survival was 52%. CONCLUSIONS: Acute kidney injury is common in Iceland and the prognosis of those with severe AKI is dismal. Majority of those patients were taking drugs that increase risk of AKI, providing a target for preventive measures.