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Table 4 Examples of big data projects related to lithium and renal function

From: Big data for bipolar disorder

Country

Description

Primary finding

Data source

Number of subjects analyzed (N)

Reference

Denmark

Examine association between long-term lithium use (≥5 years) and risk of renal and upper urinary tract cancers

Not associated with an increased risk

Danish Cancer Registry between 2000 and 2012

6447 cases matched to 259,080 controls

Pottegard et al. 2016

Denmark

Compare rates of chronic kidney disease (CKD) and end-stage CKD in patients taking lithium or other drugs for BP

Maintenance treatment with lithium or anticonvulsants increases rate of CKD, but lithium is not associated with increased rate of end-stage CKD

Danish population registries 1994–2012

1,500,000 randomly selected controls, 26,731 exposed to lithium and 420,959 to anticonvulsants for any reason. 10,591 with primary diagnosis of BP

Kessing et al. 2015a

Denmark

Assess risk of renal and upper urinary tract tumors among lithium users

Not associated with an increased risk

Danish population registries 1995–2012

1,500,000 randomly selected controls, 24,272 exposed to lithium and 386,255 to anticonvulsants for any reason. 9651 with primary diagnosis of BP

Kessing et al. 2015b

Italy

Examined glomerular filtration rate (GFR) in patients with long-term lithium treatment

Lithium is a risk factor for reduced GFR. Renal dysfunction tends to appear after decades of treatment and to progress slowly. Median time to enter G3a was 25 years

Lithium register from 1980 to 2012

953 patients. Patients treated up to 33 years

Bocchetta et al. 2015

Scotland

Comparison of estimated glomerular filtration rate (eGFR) in patients recently started on lithium therapy versus those taking other medications for affective disorders

No effect of stable lithium maintenance therapy, with lithium levels in the therapeutic range, on rate of change in eGFR over time

Population of patients started on lithium therapy in Tayside between 2000 and 2011

305 in lithium group; 815 in comparator group. Mean duration of exposure 55 months

Clos et al. 2015

Sweden

Determine prevalence and extent of kidney damage during course of long-term lithium treatment

About one-third of patients treated for ≥10 years had evidence of chronic renal failure; only 5 % severe. Continuous monitoring of kidney function is required

Lab data from all Gothenburg area public hospitals and clinics

630 patients starting lithium after 1980 with ≥10 years of cumulative lithium treatment

Aiff et al. 2015

UK

Compared lab measures of renal, thyroid and parathyroid function in those with at least two lithium measurements versus those with no lithium measurements

Lithium treatment associated with decline in renal function, hypothyroidism and hypercalcemia. Women <60 years with lithium concentrations higher than median at greatest risk. Long-term monitoring needed

Lab data from Oxfordshire area between 1985 and 2014

2795 ≥18 years with at least two lithium measurements; 689,228 controls

Shine et al. 2015

UK

Assess association between lithium use and renal failure in patients with bipolar disorder

Ever use of lithium was associated with an increased risk of renal failure (adjusted hazard ratio 2.5). Absolute risk of renal failure was age dependent and small

General practice research database from 418 practices between 1990 and 2007

6360 with BP; 2496 lithium users; 3864 non-users

Close et al. 2014

US

Possibility of stratifying risk for renal insufficiency among lithium treated patients

Use of lithium more than once daily; lithium levels >0.6 mEq/l, and use of first generation AP independently associated with risk

EMR records from large healthcare system 2006–2013

1445 lithium users with renal insufficiency; 4306 lithium users for comparison

Castro et al. 2015b