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Background. Cardiovascular disease and chronic kidney disease (CKD) progression pathophysiology are similar. We investigated associations of cardiometabolic protein expression and pathways with kidney function decline in older adults with advanced CKD referred for nephrology assessment.

Methods. Two plasma proteomic panels analysed at baseline (Olink® cardiometabolic T96 and cardiovascular II T96, Uppsala, Sweden) and longitudinal estimated glomerular filtration rate (eGFR) data from European adults aged >65 years with a single eGFR of <20 mL/min/1.73 m2 [European Quality (EQUAL) Study] were used to explore mechanisms of CKD progression. Protein-slope associations were estimated using generalized linear mixed-effects models and with a false-discovery rate P < .05 taken to validation to verify the effect size of the association. Proteins were further modularized into biological pathways using pathway enrichment analysis.

Results. A discovery sub-cohort of 238 complete-case participants from Germany, the UK and Poland (median age 76 years, 41% female sex, median baseline eGFR 17.8 mL/min/1.73 m2) were included and 246 participants from Sweden formed the validation sub-cohort (median age 75 years, 28% female, median baseline eGFR 17.5 mL/min/1.73 m2). Of the 175 analysed proteins, higher expression levels of Receptor-type tyrosine-protein phosphatase S [–15.4% change in eGFR per year per doubling of protein expression; 95% confidence interval (CI) –23.5%, –7.6%], Insulin-like growth factor binding protein 6 (–7.9%; 95% CI –12.3%, –3.5%) and Ficolin 2 (–7.4%; 95% CI –12.0%, –2.8%) showed a validated association with eGFR decline.

Conclusions. Higher expression levels of proteins and biological pathways involving fibrogenesis and the complement cascade were found to be associated with kidney function loss. However, study limitations and unavailability of concurrent kidney cellular proteomic signatures necessitate further study.

Background: Long-term lithium treatment decreases kidney function. However, it remains unclear whether stopping lithium improves kidney function.

Objectives: To study kidney function in patients who stopped and subsequently restarted lithium treatment.

Methods: Mirror-image design using data from the LiSIE retrospective cohort study. The mirror was set to when lithium was stopped with a 5-year pre- and post-mirror period. Adult patients with bipolar, schizoaffective disorder or unipolar depression, who had lithium ≥4.5 years in the pre-mirror period, were included. Creatinine measurements were available from 1997 to 2017. The main outcome was the difference in mean annual change of the estimated glomerular filtration rate (eGFR) adjusted for sex, hypertension and diabetes mellitus.

Results: A total of 168 participants (94 women, 74 men) were included. Mean annual eGFR change was −1.58 (−1.87 to −1.28) mL/min/1.73 m²/year before and −0.023 (−0.49 to +0.44) mL/min/1.73 m²/year after lithium discontinuation (p < 0.0001 for difference). The improvement was 0.77 (0.35–1.20) mL/min/173 m²/year in participants with eGFR >60 mL/min/1.73 m², and 3.03 (2.15–3.92) mL/min/1.73 m²/year for participants with eGFR <30 mL/min/1.73 m². The effect was persistent over the 5-year post-mirror study period. For participants restarting lithium, the mean annual eGFR change was −1.71 (−2.26 to −1.16) mL/min/1.73 m²/year, a setback compared to their lithium-free post-mirror period (p < 0.0001). We did not see any difference compared to the pre-mirror period (p = 0.51).

Conclusions: Stopping lithium slowed down mean eGFR decline. This effect was more pronounced in participants with lower eGFR at the time of lithium discontinuation. In participants who restarted lithium, the annual decline of eGFR reverted to pre-lithium discontinuation levels.

Gene silencing therapy is an effective treatment for amyotrophic lateral sclerosis (ALS) patients carrying mutations in the superoxide dismutase-1 (SOD1) gene aiming to reduce noxious forms of SOD1 in the central nervous system (CNS). The normal steady-state level of SOD1 protein in human CNS is therefore of interest but is contested. In this work we have analyzed SOD1 protein content, total protein content, and SOD1 enzymatic activity in six areas of the CNS as well as in four peripheral tissues from sporadic and familial ALS patients and non-ALS controls. Our results show that SOD1 in the human CNS constitutes around 100 μg/g wet weight corresponding to about 0.16% of the total protein in the studied areas. Of the peripheral tissues analyzed, kidney and erythrocytes contain roughly equal amounts, liver higher, and skeletal muscle lower levels of SOD1 compared to the CNS. This data shows SOD1 protein levels around 10 times lower compared to previously published figures. However, SOD1 can still be considered an abundant protein considering that > 12 000 proteins are expressed in human cells. There was no difference in SOD1 protein content between sporadic or familial ALS patients and control individuals. The level and activity of SOD1 are not deviating in the areas of the CNS that are most vulnerable to ALS. Instead, insufficient control of SOD1 structure and aggregation could be important factors behind the vulnerability of motor areas to SOD1 proteotoxicity. (Figure presented.).

Objective: The prevalence of chronic kidney disease (CKD) is increasing globally, and CKD is closely related to cardiovascular disease (CVD). CKD and CVD share several risk factors (RF), such as diabetes, hypertension, obesity and smoking, and the prevalence of these RF has changed during the last decades, and we aimed to study the effect on renal function over time.

Design: Repeated cross-sectional population-based studies.

Setting: The two Northern counties (Norr- and Västerbotten) in Sweden.

Participants: Within the MONitoring Trends and Determinants of CArdiovascular Disease (MONICA) study, seven surveys were performed between 1986 and 2014, including participants aged 25-64 years (n=10 185).

Interventions: None.

Measures: Information on anthropometry, blood pressure and cardiovascular risk factors was collected. Creatinine and cystatin C were analysed in stored blood samples and the estimated glomerular filtration rate (eGFR) calculated using the creatinine-based Lund-Malmö revised and Chronic Kidney Disease Epidemiology Collaboration (eGFR crea) equations as well as the cystatin C-based Caucasian, Asian, Paediatric and Adult cohort (CAPA) equation (eGFR cysC). Renal function over time was analysed using univariable and multivariable linear regression models.

Results: Renal function, both eGFR crea and eGFR cysC, decreased over time (both p<0.001) and differed between counties and sexes. In a multivariable analysis, study year remained inversely associated with both eGFR crea and eGFR cysC (both p<0.001) after adjustment for classical cardiovascular RF.

Conclusion: Renal function has deteriorated in Northern Sweden between 1986 and 2014.

Background: The clinical relevance of lithium nephropathy is subject to debate. Kidney function decreases with age and comorbidities, and this decline might lead to attribution bias when erroneously ascribed to lithium. We aimed to investigate whether patients with bipolar or schizoaffective disorder had faster decline in estimated glomerular filtration rate (eGFR) compared with the general population, whether observed differences in the steepness of the decline were attributable to lithium, and whether such changes depended on the length of lithium exposure.

Methods: In this cross-sectional cohort study, we used clinical data from the Lithium–Study into Effects and Side-effects (LiSIE) retrospective cohort study, which included patients with bipolar disorder or schizoaffective disorder whose medical records were reviewed up to Dec 31, 2017, and the WHO Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, covering a representative sample of the general population in northern Sweden aged 25–74 years. The primary outcome was the age-associated decline of creatinine-based eGFR, assessed using linear regression. We adjusted for sex and grouped for different lengths of lithium exposure (never or <1 year, 1–5 years, >5–10 years, and >10 years). For patients with moderate-to-severe kidney disease we identified the underlying nephropathy in the case records.

Findings: From LiSIE, we included 785 patients (498 [63%] female and 287 [37%] male), with a mean age of 49·8 years (SD 13·2; range 25–74). From MONICA, we included 1549 individuals (800 [52%] female and 749 [48%] male), with a mean age of 51·9 years (13·8; 25–74). No ethnicity data were collected. Adjusted for duration of lithium exposure, eGFR declined by 0·57 mL/min/1·73 m2/year (95% CI 0·50–0·63) in patients with bipolar disorder or schizoaffective disorder and by 0·57 mL/min/1·73 m2/year (0·53–0·61) in the reference population. Lithium added 0·54 mL/min/1·73 m2 (0·43–0·64) per year of treatment (p<0·0001). After more than 10 years on lithium, decline was significantly steeper than in all other groups including the reference population (p<0·0001). Lithium nephropathy was judged to be the commonest cause of moderate-to-severe chronic kidney disease, but comorbidities played a role. The effect of lithium on eGFR showed a high degree of inter-individual variation.

Interpretation: Steeper eGFR decline in patients with bipolar disorder or schizoaffective disorder can be attributed to lithium, but the trajectory of kidney function decline varies widely. Comorbidities affecting kidneys should be treated assertively as one possible means to affect the trajectory. In patients with a fast trajectory, a trade-off is required between continuing lithium to treat mental health problems and discontinuing lithium for the sake of renal health.

Funding: Norrbotten County Research and Learning Fund Sweden, Visare Norr (Northern County Councils Regional Federation Fund), Swedish Kidney Foundation (Njurfonden), Swedish Kidney Association (Njurförbundet), Norrbotten section.

Translation: For the Swedish translation of the Summary see Supplementary Materials section.

Microbiota has been associated with autoimmune diseases, with nasal Staphylococcus aureus being implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV). Little is known about the role of oral microbiota in AAV. In this study, levels of IgG antibodies to 53 oral bacterial species/subspecies were screened using immunoblotting in plasma/serum in pre-symptomatic AAV-individuals (n = 85), matched controls, and established AAV-patients (n = 78). Saliva microbiota from acute-AAV and controls was sequenced from 16s rDNA amplicons. Information on dental status was extracted from a national register. IgG levels against oral bacteria were lower in established AAV versus pre-AAV and controls. Specifically, pre-AAV samples had, compared to controls, a higher abundance of periodontitis-associated species paralleling more signs of periodontitis in established AAV-patients than controls. Saliva microbiota in acute-AAV showed higher within-sample diversity but fewer detectable amplicon-sequence variants and taxa in their core microbiota than controls. Acute-AAV was not associated with increased abundance of periodontal bacteria but species in, e.g., Arthrospira, Staphylococcus, Lactobacillus, and Scardovia. In conclusion, the IgG profiles against oral bacteria differed between pre-AAV, established AAV, and controls, and microbiota profiles between acute AAV and controls. The IgG shift from a pre-symptomatic stage to established disease cooccurred with treatment of immunosuppression and/or antibiotics.

Dietylenglykol är en toxisk alkohol som i detaljhandeln främst förekommer i bromsvätska. 

Förloppet vid dietylenglykolförgiftning skiljer sig i viktiga avseenden från de mera kända toxiska alkoholerna etylenglykol och metanol.

Dietylenglykolförgiftningen ger få intiala symtom men kan med fördröjning orsaka irreversibla njurskador och neurologiska bortfallssymtom. 

Globalt har massförgiftningar inträffat, ibland med hundratals dödsfall, där dietylenglykol använts som lösningsmedel i läkemedel. 

Här presenteras det första kända svenska fallet av dietylenglykolförgiftning, där intag av en större mängd bromsvätska ledde till anuri, leverpåverkan, kranialnervs­påverkan och polyneuropati.

Diethylene glycol poisoning – the first known Swedish case

A woman in her sixties presented at the Emergency department with nausea, flank pain and profuse vomiting. She had an anion-gap metabolic acidosis, elevated liver enzymes and a pronounced renal failure with creatinine 1997 µmol/L (22,6 mg/dl). She was admitted and treated with haemodialysis. On hospital day 5 a bilateral facial palsy, blindness and a moderate generalized weakness rapidly developed. The patient now revealed that she had consumed about 2 dl of brake fluid with a high content of diethylene glycol about a week before hospital admission. Diethylene glycol poisoning typically causes irreversible kidney failure and demyelinating nerve damage in severe cases. The early and debilitating metabolic acidosis seen in ethylene glycol poisoning seems to be absent in diethylene glycol poisoning and patients often present late. This is the first known Swedish case of symptomatic diethylene glycol poisoning. Internationally, during the last century, several mass poisonings have been caused by diethylene glycol contaminated pharmaceutical products.

Aims: Glomerular filtration rate is an important factor in management of heart failure (HF). Our objective was to validate eight creatinine-based equations for estimating glomerular filtration rate (eGFR) in an HF population against measured glomerular filtration rate.

Methods and results: One hundred forty-six HF patients (mean age 68 +/- 13 years, mean left ventricular ejection fraction 45% +/- 15) within a single-centre hospital that underwent Cr-51-EDTA clearance between 2010 and 2018 were included in this retrospective study. eGFR was estimated by means of Cockcroft-Gault ideal and actual weight, the Modification of Diet in Renal Disease Study (MDRD), simplified MDRD with isotope dilution mass spectroscopy traceable calibration, the Chronic Kidney Disease Epidemiology Collaboration, revised Lund-Malmo, full age spectrum, and the Berlin Initiative Study 1. Mean measured glomerular filtration rate was 42 mL/min/1.73 m(2). Pearson's correlation coefficient (r) had the highest precision for MDRD (r = 0.9), followed by revised Lund-Malmo (r = 0.88). All equations except MDRD (mean difference -4.8%) resulted in an overestimation of the renal function. The accuracy was below 75% for all equations except MDRD.

Conclusions: None of the exclusively creatinine-based methods was accurate in predicting eGFR in HF patients. Our findings suggest that more accurate methods are needed for determining eGFR in patients with HF.

Background: An arteriovenous fistula (AVF) is the first choice when considering access for haemodialysis (HD).When a forearm AVF fails an upper arm AVF is a frequent subsequent dialysis access option. The latter may causecardiac strain. NT-pro-B-type natriuretic peptide (NT-NT-proBNP) is a marker used to estimate volume overload andcardiac strain.This case report shows the benefit of using longitudinal individual follow-up of pre-dialysis NT-proBNP in clinicalpractice to detect changes in cardiac condition that may be due to high-output AVF.

Case presentation: An 18 years old patient performed HD via an upper arm AVF before he was admitted to ourunit. NT-proBNP was above the upper detection level of 70,000 ng/L. Echocardiography revealed a left-ventricularcardiac insufficiency. Interdialytic weight gain (IDWG) was above 5%. He was instructed to lower fluid intake andIDWG towards 2%. Four months later NT-proBNP surpassed 70,000 ng/L again. Flow in the brachial artery was at3034 ml/min. Reconstructive surgery of the AVF did not reduce flow and NT-proBNP in the long run. Clinically, heworsened to NYHA class III-IV. It was decided to close the upper arm AVF and to replace it with a lower arm AVFleading to a reduced artery flow of 1344 mL/min. The clinical condition successively recovered and NT-proBNPdecreased to 7000 ng/L.

Conclusions: Pre-dialysis NT-proBNP should be considered as a suitable routine marker for cardiac strain such ascaused by high-output AVF besides variables such as IDWG. Brachial artery flow besides AVF flow measurement ishelpful.