Lifetime risk of severe kidney disease in lithium-treated patients: a retrospective study.

BACKGROUND: Lithium is an essential psychopharmaceutical, yet side effects and concerns about severe renal function impairment limit its usage. AIMS: Our objectives were to quantify the occurrence of chronic kidney disease stage 4 or higher (CKD4 +) within a lithium-treated population, using age- and time-specific cumulative incidence and age-specific lifetime risk as measures of disease occurrence. Additionally, we aimed to investigate the association between the duration of lithium treatment and the risk of CKD4 + . METHODS: We identified patients from the Sahlgrenska University Hospital's laboratory database. We conducted a retrospective cohort study employing cumulative incidence functions that account for competing deaths to estimate cumulative and lifetime risk of CKD4 + . A subdistribution hazards model was employed to explore baseline covariates. For measuring the association between the duration of lithium treatment and CKD4 + occurrence, we used a matched 1:4 case-control study design and logistic regression. RESULTS: Considering a 90-year lifetime horizon, the lifetime risk of CKD4 + for patients initiating lithium treatment between ages 55 and 74 ranged from 13.9% to 18.6%. In contrast, the oldest patient group, those starting lithium at 75 years or older, had a lower lifetime risk of 5.4%. The 10-year cumulative risk for patients starting lithium between ages 18 and 54 was minimal, ranging from 0% to 0.7%. Pre-treatment creatinine level was a predictive factor, with a hazard ratio of 4.6 (95% CI 2.75-7.68) for values within the upper third of the reference range compared to the lower third. Moreover, twenty or more years of lithium exposure showed a strong association with an increased risk of CKD4 + compared to 1-5 years of lithium use, with an odds ratio of 6.14 (95% CI 2.65-14.26). CONCLUSIONS: The risk of CKD4 + among lithium-treated patients exhibited significant age-related differences. Patients under 55 years old had negligible 10-year risk, while the lifetime risk for those aged 75 and older was limited. Duration of lithium treatment, especially exceeding 20 years, emerged as a significant risk factor. For individual risk assessment and prediction, consideration of age, pre-treatment creatinine levels, and the chosen time horizon for prediction is essential.

Causal inference in survival analysis under deterministic missingness of confounders in register data.

Long-term register data offer unique opportunities to explore causal effects of treatments on time-to-event outcomes, in well-characterized populations with minimum loss of follow-up. However, the structure of the data may pose methodological challenges. Motivated by the Swedish Renal Registry and estimation of survival differences for renal replacement therapies, we focus on the particular case when an important confounder is not recorded in the early period of the register, so that the entry date to the register deterministically predicts confounder missingness. In addition, an evolving composition of the treatment arms populations, and suspected improved survival outcomes in later periods lead to informative administrative censoring, unless the entry date is appropriately accounted for. We investigate different consequences of these issues on causal effect estimation following multiple imputation of the missing covariate data. We analyse the performance of different combinations of imputation models and estimation methods for the population average survival. We further evaluate the sensitivity of our results to the nature of censoring and misspecification of fitted models. We find that an imputation model including the cumulative baseline hazard, event indicator, covariates and interactions between the cumulative baseline hazard and covariates, followed by regression standardization, leads to the best estimation results overall, in simulations. Standardization has two advantages over inverse probability of treatment weighting here: it can directly account for the informative censoring by including the entry date as a covariate in the outcome model, and allows for straightforward variance computation using readily available software.

The low risk for early renal damage during lithium treatment has not changed over time.

BACKGROUND: Modern lithium management guidelines were introduced to improve the renal prognosis of lithium patients. AIMS: To examine whether prospects for severe renal impairment (defined as chronic kidney disease at least stage 4 (CKD4)), in long-term lithium patients, have changed over time after the introduction of lithium monitoring guidelines. METHODS: The time to and hazard for CKD4 were compared between three patient cohorts who started long-term lithium in three consecutive decades: 1980s, 1990s and 2000s. The follow-up time was 10 years after completion of 1-year treatment. The data were collected from Sahlgrenska University Hospital's laboratory database. RESULTS: In all, 2169 patients were included: 623 in Cohort 1 (started lithium during 1980s), 874 in Cohort 2 (1990s) and 672 in Cohort 3 (2000s). Compliance with lithium monitoring guidelines improved, and mean serum lithium decreased, through the cohorts. In all, 22 patients developed CKD4 during follow-up. The time to CKD4 was the same in all three cohorts (overall: 10.96 years, 95% confidence interval: 10.94-11 years). Age and serum creatinine concentration at start were significant risk factors, while sex had no prognostic value. After adjusting for the significant covariates, there was no statistically significant difference in the hazard for CKD4 between the three cohorts. CONCLUSION: The risk for severe renal damage during the first decade of long-term lithium is low, but has not changed over time. Our data suggest that improved compliance with lithium guidelines is not reflected in less risk for severe renal damage.

Trial emulation and survival analysis for disease incidence registers: A case study on the causal effect of pre-emptive kidney transplantation.

When drawing causal inference from observed data, failure time outcomes present additional challenges of censoring often combined with other missing data patterns. In this article, we follow incident cases of end-stage renal disease to examine the effect on all-cause mortality of starting treatment with transplant, so-called pre-emptive kidney transplantation, vs starting with dialysis possibly followed by delayed transplantation. The question is relatively simple: which start-off treatment is expected to bring the best survival for a target population? To address it, we emulate a target trial drawing on the long term Swedish Renal Registry, where a growing common set of baseline covariates was measured nationwide. Several lessons are learned which pertain to long term disease registers more generally. With characteristics of cases and versions of treatment evolving over time, informative censoring is already introduced in unadjusted Kaplan-Meier curves. This leads to misrepresented survival chances in observed treatment groups. The resulting biased treatment association may be aggravated upon implementing IPW for treatment. Aware of additional challenges, we further recall how similar studies to date have selected patients into treatment groups based on events occurring post treatment initiation. Our study reveals the dramatic impact of resulting immortal time bias combined with other typical features of long-term incident disease registers, including missing covariates during the early phases of the register. We discuss feasible ways of accommodating these features when targeting relevant estimands, and demonstrate how more than one causal question can be answered relying on the no unmeasured baseline confounders assumption.

Starting lithium in patients with compromised renal function - is it wise?

BACKGROUND: Little is known of the risks involved for patients who, at the start of lithium treatment, already have compromised renal function. AIMS: To assess the risk of developing severe renal impairment (chronic kidney disease (CKD) 4-5) among those patients and to explore predictors for the progression. METHODS: A retrospective longitudinal cohort study using data from Sahlgrenska University Hospital's laboratory database 1981-2017. We compared the risk of developing CKD 4-5 in two patient cohorts: an exposed cohort of 83 patients who had high serum creatinine prior to start of lithium and a reference cohort of 83 patients with normal serum creatinine, matched by gender, duration of lithium treatment and age at the start of lithium treatment. The patients' medical charts were reviewed and the Swedish Renal Registry was used to identify patients with renal replacement therapy. RESULTS: There were no significant differences between the exposed and reference cohorts with respect to our matching criteria. Almost half the patients in the exposed cohort versus only 10% of the reference patients progressed to CKD 4-5 (HR 6.7, 95%CI 3.1-14.3, p < 0.001) during a mean observation time of more than 10 years. The progressors were older at the start of lithium treatment and were characterised by a higher burden of comorbid somatic diseases, in particular cardiovascular diseases. CONCLUSIONS: Compromised renal function prior to initiating lithium treatment increases the risk of developing severe renal impairment. Monitoring of renal function should include somatic comorbidity among older patients.

Oral mucosal lesions and risk of all-cause and cardiovascular mortality in people treated with long-term haemodialysis: The ORAL-D multinational cohort study.

BACKGROUND: Chronic kidney disease is a risk factor for oral diseases, which may be associated with premature death. We evaluated the risk of all-cause and cardiovascular mortality associated with oral mucosal lesions in adults with kidney failure treated with long-term haemodialysis. METHODS: Oral mucosal lesions (herpes, ulceration, neoformation, white lesion, red lesion, oral candidiasis, geographical tongue, petechial lesions, and fissured tongue) were evaluated within the Oral Diseases in Haemodialysis (ORAL-D) study, a multinational cohort study of 4726 haemodialysis adults. We conducted cox regression analyses adjusted for demographic and clinical variables to evaluate the association with all-cause and cardiovascular mortality. RESULTS: Overall, 4205 adults (mean age 61.6 ± 15.6 years) underwent oral mucosal examination with 40% affected by at least one lesion. The prevalence of oral lesions was (in order of frequency): oral herpes 0.5%, mucosal ulceration 1.7%, neoformation 2.0%, white lesion 3.5%, red lesion 4.0%, oral candidiasis 4.6%, geographical tongue 4.9%, petechial lesions 7.9%, and fissured tongue 10.7%. During median follow-up of 3.5 years, 2114 patients died (1013 due to cardiovascular disease). No association was observed between any individual oral lesion and all-cause or cardiovascular mortality when adjusted for comorbidities, except for oral candidiasis, which was associated with all-cause mortality (adjusted hazard ratio 1.37, 95% CI 1.00 to 1.86) and cardiovascular mortality (adjusted hazard ratio 1.64, 95% CI 1.09 to 2.46). CONCLUSION: Oral mucosal lesions are prevalent in haemodialysis patients. Oral candidiasis appears to be a risk factor for death due to cardiovascular diseases.

A prospective observational study of iron isomaltoside in haemodialysis patients with chronic kidney disease treated for iron deficiency (DINO).

BACKGROUND: Iron deficiency is frequent in haemodialysis (HD) patients with chronic kidney disease (CKD), and intravenous iron is an established therapy for these patients. This study assessed treatment routine, effectiveness, and safety of iron isomaltoside (IIM) 5% (Diafer®) in a HD cohort. METHODS: This prospective observational study included 198 HD patients converted from iron sucrose (IS) and treated with IIM according to product label and clinical routine. Data for IIM were compared to historic data for IS in 3-month intervals. The primary endpoint was to show non-inferiority for IIM versus IS in haemoglobin (Hb) maintenance. RESULTS: Most patients (> 60%) followed a fixed low-dose iron treatment protocol. Three minutes were required for preparation and administration of IIM. Erythropoiesis-stimulating agent (ESA) was used in > 80% of patients during both IIM and IS phases. The maintenance of Hb was similar with both iron drugs; the mean Hb level was 11 g/dL, and the mean change of 0.3 g/dL (95% confidence interval: 0.1, 0.5) for IIM 0-3 months compared to IS demonstrated non-inferiority. Nine adverse drug reactions were reported in 2% of patients administered IIM. All patients had uneventful recoveries. The frequency of metallic taste was higher with IS compared to IIM (34% versus 0.5%, p < 0.0001). CONCLUSIONS: IIM is effective and well tolerated by CKD patients on HD. IIM was non-inferior to IS in maintenance of Hb, and had similar ESA requirements. The fast-push injection of IIM may enable logistical benefits in clinical practice, and the low frequency of metallic taste contributes to patient convenience. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02301026, study registered November 25, 2014.

Cardiovascular comorbidity increases the risk for renal failure during prophylactic lithium treatment.

BACKGROUND: The development of lithium-associated kidney damage is still a matter of controversy. We have addressed this question by investigating the role of somatic comorbidity for developing kidney failure in lithium treated patients. METHODS: The study group comprised of 1741 adult patients with normal creatinine levels at the start of lithium treatment. Patients who developed severe renal failure (CKD stages 4-5, n = 109), were matched by sex, time on lithium and age at start of lithium, with 109 controls (CKD stages 1-2) that did not develop severe renal failure. RESULTS: Patients in CKD 4-5 did not differ significantly from controls (CKD 1-2) in sex (females/males were 76/33 in both groups), time on lithium (mean 9.8 years, SD 6.4; vs. 9.6, SD 6.2) or age at start of lithium (mean 61.6 years, SD 13.4; vs. 60.5 years, SD 12.3), respectively. However, comparisons between groups showed a significantly higher prevalence of somatic comorbidity (p < 0.001), especially cardiovascular diseases (p < 0.003), among patients in CKD 4-5. LIMITATIONS: Patients in our study group were relatively old and the findings are therefore not generalizable to patients starting lithium at an early age. The retrospective design, relying on available charts, did not allow to grade severity of comorbid conditions other than need for hospitalisation or chronic drug treatment. CONCLUSIONS: Our findings emphasize the role of somatic comorbidity for renal damage in lithium treated patients and especially the role of cardiovascular comorbidity. Monitoring of somatic comorbidity should be taken into account in treatment recommendations and safety routines in long-term prophylactic lithium treatment.

Decreasing Cumulative Incidence of End-Stage Renal Disease in Young Patients With Type 1 Diabetes in Sweden: A 38-Year Prospective Nationwide Study.

OBJECTIVE: Diabetic nephropathy is a serious complication of type 1 diabetes. Recent studies indicate that end-stage renal disease (ESRD) incidence has decreased or that the onset of ESRD has been postponed; therefore, we wanted to analyze the incidence and time trends of ESRD in Sweden. RESEARCH DESIGN AND METHODS: In this study, patients with duration of type 1 diabetes >14 years and age at onset of diabetes 0-34 years were included. Three national diabetes registers were used: the Swedish Childhood Diabetes Register, the Diabetes Incidence Study in Sweden, and the National Diabetes Register. The Swedish Renal Registry, a national register on renal replacement therapy, was used to identify patients who developed ESRD. RESULTS: We found that the cumulative incidence of ESRD in Sweden was low after up to 38 years of diabetes duration (5.6%). The incidence of ESRD was lower in patients with type 1 diabetes onset in 1991-2001 compared with onset in 1977-1984 and 1985-1990, independent of diabetes duration. CONCLUSIONS: The risk of developing ESRD in Sweden in this population is still low and also seems to decrease with time.

Compliance with the safety guidelines for long-term lithium treatment in Sweden.

BACKGROUND: Lithium has been used for more than 50 years and guidelines for treatment monitoring have been documented in Sweden since the beginning of the 1980s. AIMS: The aim of this study was to describe compliance over time with the Swedish guidelines for long-term lithium treatment. METHODS: The study material was obtained from Sahlgrenska University Hospital's laboratory database. We analysed data (serum lithium and serum creatinine) of adult patients treated with lithium between 1981 and 2010, and determined compliance with guidelines and serum lithium levels over time. RESULTS: Our study material included 2841 patients and 25,300 treatment-years. The compliance with guidelines' recommendations regarding lithium and creatinine monitoring increased from 36% in 1981 to 68% in 2010. Women were on average 2% more compliant than men ( p < 0.01). Most lithium samples (87-94%) were within recommended intervals throughout the study period. The average lithium level decreased from 0.70 mmol/L in 1981 to 0.58 mmol/L in 2001, and remained stable thereafter. CONCLUSIONS: Compliance with lithium monitoring guidelines improved slowly but steadily over time. It took three decades to reach a compliance rate of just below 70%. Gender differences were small, but with a significantly better compliance rate for women. Serum lithium was kept within the recommended target interval to a large extent, throughout the study period.

The prevalence and correlates of low sexual functioning in women on hemodialysis: A multinational, cross-sectional study.

Sexual dysfunction may affect 80% of women in hemodialysis. However the specific patterns and clinical correlates of sexual functioning remain poorly described. The aim of this study was to assess prevalence and correlates of the individual domains of sexual functioning in women treated with hemodialysis. We recruited, into this multinational cross-sectional study, women treated with long-term hemodialysis (Collaborative Working Group on Depression and Sexual dysfunction in Hemodialysis study). Self-reported domains of sexual functioning were assessed by the Female Sexual Function Index, which is routinely administered within the network of dialysis patients followed by the working group. Lower scores represented lower sexual functioning. Socio-demographic and clinical correlates of each domain of sexual functioning were identified by stepwise multivariable linear regression. Sensitivity analyses were restricted to women who reported being sexually active. We found that of 1309 enrolled women, 659 (50.3%) provided complete responses to FSFI survey questions and 232 (35%) reported being sexually active. Overall, most respondents reported either no sexual activity or low sexual functioning in all measured domains (orgasm 75.1%; arousal 64.0%; lubrication 63.3%; pain 60.7%; satisfaction 60.1%; sexual desire 58.0%). Respondents who were waitlisted for a kidney transplant reported scores with higher sexual functioning, while older respondents reported scores with lower functioning. The presence of depression was associated with worse lubrication and pain scores [mean difference for depressed versus non-depressed women (95% CI) -0.42 (-0.73 to -0.11), -0.53 (-0.89 to -0.16), respectively] while women who had experienced a previous cardiovascular event reported higher pain scores [-0.77 (-1.40- to -0.13)]. In conclusion, women in hemodialysis reported scores consistent with marked low sexual functioning across a range of domains; the low functioning appeared to be associated with comorbidity.

Periodontitis and early mortality among adults treated with hemodialysis: a multinational propensity-matched cohort study.

BACKGROUND: Periodontitis is associated with cardiovascular mortality in the general population and adults with chronic diseases. However, it is unclear whether periodontitis predicts survival in the setting of kidney failure. METHODS: ORAL-D was a propensity matched analysis in 3338 dentate adults with end-stage kidney disease treated in a hemodialysis network in Europe and South America designed to examine the association between periodontitis and all-cause and cardiovascular-related mortality in people on long-term hemodialysis. Participants were matched 1:1 on their propensity score for moderate to severe periodontitis assessed using the World Health Organization Community Periodontal Index. A random-effects Cox proportional hazards model was fitted with shared frailty to account for clustering of mortality risk within countries. RESULTS: Among the 3338 dentate participants, 1355 (40.6%) had moderate to severe periodontitis at baseline. After using propensity score methods to generate a matched cohort of participants with periodontitis similar to those with none or mild periodontal disease, moderate to severe periodontitis was associated with a lower risk of all-cause (9.1 versus 13.0 per 100 person years, hazard ratio 0.74, 95% confidence interval 0.61 to 0.90) and cardiovascular (4.3 versus 6.9 per 100 person years, hazard ratio 0.67, 0.51 to 0.88) mortality. These associations were not changed substantially when participants were limited to those with 12 or more natural teeth and when accounting for competing causes of cardiovascular death. CONCLUSION: In contrast to the general population, periodontitis does not appear to be associated with an increased risk of early death in adults treated with hemodialysis.

Depression and all-cause and cardiovascular mortality in patients on haemodialysis: a multinational cohort study.

Background: Depression and early death are both common in adults with Stage 5 chronic kidney disease. Studies have shown an association between depression and total mortality, but the association between depression and cardiovascular death is less certain. Methods: We conducted a prospective multinational cohort study involving adults who were treated with long-term haemodialysis within a single dialysis network between April and November 2010. Depression was considered present when patients reported a Beck Depression Inventory (BDI) II score ≥14 at baseline. Sensitivity analyses considered a BDI II score ≥20 to identify moderate depression. Multivariable Cox proportional hazards regression was used to assess adjusted hazards for all-cause and cardiovascular mortality at 12 months. Results: Three thousand and eighty-six participants in the network received the BDI II questionnaire, and 2278 (73%) provided complete responses to the survey questions. Among these, 1047 (46%) reported depression. During a mean follow-up of 11 (standard deviation: 2.5) months (2096 person-years), we recorded 175 deaths, of which 66 were attributable to cardiovascular causes. Depression (BDI score ≥14) was not associated with all-cause mortality [adjusted hazard ratio: 1.26 (95% confidence interval: 0.93­1.71)] or cardiovascular mortality [0.82 (0.50­1.34)]. When a higher BDI score (BDI score ≥20) was used to identify moderate depression, depression was associated with total mortality [1.40 (1.02­1.93)] but not cardiovascular mortality [1.05 (0.63­1.77)]. Conclusions: The association between depression and cardiovascular mortality in adults with kidney failure treated with haemodialysis is uncertain. Depression is a heterogeneous disorder and may only be a risk factor for premature death when at least of moderate severity.

Patterns of oral disease in adults with chronic kidney disease treated with hemodialysis.

BACKGROUND: Oral disease is a potentially treatable determinant of mortality and quality of life. No comprehensive multinational study to quantify oral disease burden and to identify candidate preventative strategies has been performed in the dialysis setting. METHODS: The ORAL disease in hemoDialysis (ORALD) study was a prospective study in adults treated with hemodialysis in Europe (France, Hungary, Italy, Poland, Portugal and Spain) and Argentina. Oral disease was assessed using standardized WHO methods. Participants self-reported oral health practices and symptoms. Sociodemographic and clinical factors associated with oral diseases were determined and assessed within nation states. RESULTS: Of 4726 eligible adults, 4205 (88.9%) participated. Overall, 20.6% were edentulous [95% confidence interval (CI), 19.4-21.8]. Participants had on average 22 (95% CI 21.7-22.2) decayed, missing or filled teeth, while moderate to severe periodontitis affected 40.6% (95% CI 38.9-42.3). Oral disease patterns varied markedly across countries, independent of participant demographics, comorbidity and health practices. Participants in Spain, Poland, Italy and Hungary had the highest mean adjusted odds of edentulousness (2.31, 1.90, 1.90 and 1.54, respectively), while those in Poland, Hungary, Spain and Argentina had the highest odds of ≥14 decayed, missing or filled teeth (23.2, 12.5, 8.14 and 5.23, respectively). Compared with Argentina, adjusted odds ratios for periodontitis were 58.8, 58.3, 27.7, 12.1 and 6.30 for Portugal, Italy, Hungary, France and Poland, respectively. National levels of tobacco consumption, diabetes and child poverty were associated with edentulousness within countries. CONCLUSIONS: Oral disease in adults on hemodialysis is very common, frequently severe and highly variable among countries, with much of the variability unexplained by participant characteristics or healthcare. Given the national variation and high burden of disease, strategies to improve oral health in hemodialysis patients will require implementation at a country level rather than at the level of individuals.

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.

Nutrition and dietary intake and their association with mortality and hospitalisation in adults with chronic kidney disease treated with haemodialysis: protocol for DIET-HD, a prospective multinational cohort study.

INTRODUCTION: Adults with end-stage kidney disease (ESKD) treated with haemodialysis experience mortality of between 15% and 20% each year. Effective interventions that improve health outcomes for long-term dialysis patients remain unproven. Novel and testable determinants of health in dialysis are needed. Nutrition and dietary patterns are potential factors influencing health in other health settings that warrant exploration in multinational studies in men and women treated with dialysis. We report the protocol of the "DIETary intake, death and hospitalisation in adults with end-stage kidney disease treated with HaemoDialysis (DIET-HD) study," a multinational prospective cohort study. DIET-HD will describe associations of nutrition and dietary patterns with major health outcomes for adults treated with dialysis in several countries. METHODS AND ANALYSIS: DIET-HD will recruit approximately 10,000 adults who have ESKD treated by clinics administered by a single dialysis provider in Argentina, France, Germany, Hungary, Italy, Poland, Portugal, Romania, Spain, Sweden and Turkey. Recruitment will take place between March 2014 and June 2015. The study has currently recruited 8000 participants who have completed baseline data. Nutritional intake and dietary patterns will be measured using the Global Allergy and Asthma European Network (GA(2)LEN) food frequency questionnaire. The primary dietary exposures will be n-3 and n-6 polyunsaturated fatty acid consumption. The primary outcome will be cardiovascular mortality and secondary outcomes will be all-cause mortality, infection-related mortality and hospitalisation. ETHICS AND DISSEMINATION: The study is approved by the relevant Ethics Committees in participating countries. All participants will provide written informed consent and be free to withdraw their data at any time. The findings of the study will be disseminated through peer-reviewed journals, conference presentations and to participants via regular newsletters. We expect that the DIET-HD study will inform large pragmatic trials of nutrition or dietary interventions in the setting of advanced kidney disease.

Effects of 10 to 30 years of lithium treatment on kidney function.

Long-term lithium treatment is associated with end-stage renal disease, but there is little evidence of a clinically significant reduction in renal function in most patients. We previously found that 1.5% of people who took lithium from the 1960s and 1970s developed end-stage renal disease; however, none of the patients who started after 1980 had end-stage renal disease. Here we aimed to study the prevalence and extent of kidney damage during the course of long-term lithium treatment since 1980. We retrieved serum lithium and creatinine levels from 4879 patients examined between 1 January 1981 and 31 December 2010. Only patients who started their lithium treatment during the study period and had at least 10 years of cumulative treatment were included. The study group comprised 630 adult patients (402 women and 228 men) with normal creatinine levels at the start of lithium treatment. There was a yearly increase in median serum creatinine levels already from the first year of treatment. About one-third of the patients who had taken lithium for 10-29 years had evidence of chronic renal failure but only 5% were in the severe or very severe category. The results indicate that a substantial proportion of adult patients who are treated with lithium for more than a decade develop signs of renal functional impairment, also when treated according to modern therapeutic principles. Our results emphasise that lithium treatment requires continuous monitoring of kidney function.

End-stage renal disease associated with prophylactic lithium treatment.

The primary aim of this study was to estimate the prevalence of lithium associated end-stage renal disease (ESRD) and to compare the relative risk of ESRD in lithium users versus non-lithium users. Second, the role of lithium in the pathogenesis of ESRD was evaluated. We used the Swedish Renal Registry to search for lithium-treated patients with ESRD among 2644 patients with chronic renal replacement therapy (RRT)-either dialysis or transplantation, within two defined geographical areas in Sweden with 2.8 million inhabitants. The prevalence date was December 31, 2010. We found 30 ESRD patients with a history of lithium treatment. ESRD with RRT was significantly more prevalent among lithium users than among non-lithium users (p<0.001). The prevalence of ESRD with RRT in the lithium user population was 15.0‰ (95% CI 9.7-20.3), and close to two percent of the RRT population were lithium users. The relative risk of ESRD with RRT in the lithium user population compared with the general population was 7.8 (95% CI 5.4-11.1). Out of those 30 patients, lithium use was classified, based on chart reviews, as being the sole (n=14) or main (n=10) cause of ESRD in 24 cases. Their mean age at the start of RRT was 66 years (46-82), their mean time on lithium 27 years (12-39), and 22 of them had been on lithium for 15 years or more. We conclude that lithium-associated ESRD is an uncommon but not rare complication of lithium treatment.

Renal replacement therapy due to type 1 diabetes; time trends during 1995-2010--a Swedish population based register study.

BACKGROUND: End stage renal disease (ESRD), is the most severe complication of diabetes mellitus. This population-based study analysed time trends for start of renal replacement therapy (RRT) due to type 1 diabetes compared to type 2 diabetes and other diagnoses. MATERIAL AND METHODS: We used data on patients who were registered 1995-2010 in the Swedish Renal Registry, a nationwide register covering 95 % of all patients with uraemia. The patients were analysed according to their original kidney disease. The incidence was analysed by calendar year, age at start of RRT and gender. RESULTS: Of 17389 patients who were registered, 1833 had type 1 diabetes; 65% were men. The mean age at onset of RRT for patients with type 1 diabetes was 52.8 years which increased by more than 3 years over the studied period. The number of patients in need of RRT due to type 1 diabetes decreased, while RRT due to type 2 diabetes increased during the period studied. CONCLUSIONS: The overall incidence of RRT in Sweden is rather constant over the years but the need for RRT in type 1 diabetes patients decreased and patients with type 1 diabetes tend to become older at onset of RRT.