Annotated Abstracts of Journal Articles
2014, 1st Quarter


Annotations by Paula Zimbrean, MD, FAPM
March 2014

  1. Increased risk of solid renal tumors in lithium-treated patients
  2. Association of Co-Occurring Serious Mental Illness with Emergency Hospitalization in People with Chronic Kidney Disease
  3. Motivational interviewing promotes adherence and improves wellbeing in pre-dialysis patients with advanced chronic kidney disease

PUBLICATION #1 — Psychonephrology
Increased risk of solid renal tumors in lithium-treated patients
Zaidan M, Stucker F, Stengel B, Vasiliu V, Hummel A, Landais P, Boffa JJ, Ronco P, Grünfeld JP, Servais A
Kidney Int 2014 Jan 22 [Epub ahead of print]

ANNOTATION (Paula Zimbrean)

The Findings:  One houndred seventy patients with an average lithium exposure of 21.3±10.4 years and average eGFR of 40.0 ±17.1 ml/min were included in the analysis. Frequency of renal cancer and oncocytoma was higher among lithium-treated patients than among their sex, age, eGFR-matched lithium-free patients (4.1% vs 0.3%, p=0.0002 and 2.4% vs 0%, p=0.01 respectively). Frequency of angiomyolipoma did not differ between the two groups. The incidence of renal cancer was 10.12 times higher in lithium treated patients compared with general French population.

Strengths and Weaknesses: This is a retrospective cohort study looking at the prevalence of renal tumors in 191 patients treated in a nephrology clinic who had previously received lithium treatment. One houndred seventy subjects were included in the analysis. The strengths of the study consist in the length of the lithium exposure (average 21.3 years), the accuracy of the tumor diagnosis (histologic) and the comparaison with patients with similar eGFR but without a history of lithium exposure. The study, however, does not include assessment of patients with lithium exposure and without kidney disease.

Relevance: Treatment with lithium has been well known to be associated with kidney disease in the form of tubular atrophy and interstitial fibrosis. Uncomplicated renal cysts have been reported in long-term lithium treated patients. Occurrence of renal carcinomas had been previously reported only when lithium exposure was combined with other toxic nephropathies. This study brings a very important finding suggesting renal cancer as a potential risk of long-term lithium exposure.


Cystic kidney diseases and toxic interstitial nephritis may be complicated by renal tumors. Long-term lithium intake is associated with tubulointerstitial nephritis and renal cysts but to date such an association with tumors has not been determined. We evaluated this in a retrospective study to determine whether lithium-treated patients were at higher risk of renal tumors compared with lithium-free patients with chronic kidney disease (CKD), and to the general population. Over a 16-year period, 14 of 170 lithium-treated patients had renal tumors, including seven malignant and seven benign tumors. The mean duration of lithium exposure at diagnosis was 21.4 years. The renal cancers included three clear-cell and two papillary renal cell carcinomas, one hybrid tumor with chromophobe and oncocytoma characteristics, and one clear-cell carcinoma with leiomyomatous stroma. The benign tumors included four oncocytomas, one mixed epithelial and stromal tumor, and two angiomyolipomas. The percentage of renal tumors, particularly cancers and oncocytomas, was significantly higher in lithium-treated patients compared with 340 gender-, age-, and estimated glomerular filtration rate (eGFR)-matched lithium-free patients. Additionally, the Standardized Incidence Ratio of renal cancer was significantly higher in lithium-treated patients compared with the general population: 7.51 (95% confidence interval (CI) (1.51–21.95)) and 13.69 (95% CI (3.68–35.06)) in men and women, respectively. Thus, there is an increased risk of renal tumors in lithium-treated patients.

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PUBLICATION #2 — Psychonephrology
Association of Co-Occurring Serious Mental Illness with Emergency Hospitalization in People with Chronic Kidney Disease
McPherson S, Barbosa-Leiker C, Daratha K, Short R, McDonell MG, Alicic R, Roll J, Tuttle K
Am J Nephrol 2014 Mar 19; 39(3):260-267

ANNOTATION (Paula Zimbrean)

The Finding:  Patients with comorbid CKD and SMI had significantly higher rate of re-hospitalizations (HR 1.36, CI=1.24-1.48, p<0.001) compared to all other cohorts. The presence of SMI did not correlate with increased death rate in patients with CKD (p=0.19).

Strengths and Weaknesses: The main strength of this study consists in the high number of subjects (31,166 patients with CKD, 20,167 patients with SMI, 717 patients with co-occurring SMI and CKD, and 548,532 patients without SMI or CKD). The study analyzed the medical reasons for hospitalizations (heart disease, acute kidney injury, pneumonia, chronic obstructive pulmonary disease); it did not control for psycho-social precipitants of hospitalization (insurance, homelessness, non-adherence, treated versus untreated mental illness).

Relevance: This study supports other findings that comorbid psychiatric illness may increase the rate of medical hospitalizations.


Background/Aims: Chronic kidney disease (CKD) and serious mental illness (SMI) are both associated with an increased risk for repeated hospitalization. The objective of this study was to determine if co-occurring SMI exacerbates the risk for subsequent hospitalization, particularly through the emergency department (ED), among people with CKD.

Methods: People hospitalized in Washington State from April 2006 to December 2008 were separated into cohorts with diagnoses of CKD (n = 31,166), SMI (defined by schizophrenia and/or mood disorder; n = 20,167) or CKD with co-occurring SMI (n = 717), and a reference cohort without either diagnosis (n = 548,532). Main outcomes were rehospitalization for condition(s) other than mental illness: (1) through the ED; (2) any admission, and (3) admission resulting in death. Cox regression was used to analyze time to main outcomes controlling for prespecified covariates associated with rehospitalization.

Results: The risk of rehospitalization via the ED was increased for people with CKD (hazard ratio, HR = 1.24, 95% confidence interval, CI = 1.21-1.28, p < 0.001) and co-occurring SMI (HR = 1.33, 95% CI = 1.29-1.38, p < 0.001) cohorts, but was significantly greater in the combined cohort (HR = 1.55, 95% CI = 1.40-1.73, p < 0.001). Similarly, the risk of any rehospitalization was increased for CKD (HR = 1.21, 95% CI = 1.17-1.25, p < 0.001) and co-occurring SMI (HR = 1.14, 95% CI = 1.11-1.17, p < 0.001) cohorts, while a significantly greater risk was observed for the combined cohort (HR = 1.36, 95% CI = 1.24-1.48, p < 0.001). The risk of rehospitalization resulting in death was not significantly increased in the combined cohort.

Conclusion: In people with CKD, co-occurring SMI increased the risk of experiencing rehospitalization, particularly through the ED. Studies of strategies to address SMI in the CKD population are needed to mitigate the risk of repeat hospital admissions.

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PUBLICATION #3 — Psychonephrology
Motivational interviewing promotes adherence and improves wellbeing in pre-dialysis patients with advanced chronic kidney disease

García-Llana H, Remor E, Del Peso G, Celadilla O, Selgas R

J Clin Psychol Med Settings 2014 Mar; 21(1):103-15

ANNOTATION (Paula Zimbrean)

The Finding:
Motivational enhancement psychotherapy centered around participation in treatment, increased medication adherence, and biological markers of CKD pre-dialysis (p<0.01).

Strengths and Limitations: This study evaluated prospectively a psychotherapeutic intervention aimed at promoting medical adherence in 42 patients with CKD. The selection criteria included age over 18, diagnosis of CKD pre-dialysis treatment, GFT <= 20ml/min, fluent in Spanish. Measurements of treatment adherence, stages of behavior change, depression, anxiety, and quality of life were administered before and after the intervention. The main limitations of the study are lack of a control group and lack of an objective measure of medication adherence (such as pill or pill bottle marker).

Relevance: This study indicates that motivational enhancement therapy may constitute an effective intervention in a common problem: non adherence with medical treatment in patients with CKD.


Low rates of adherence to medical treatments and adverse emotional states are a widespread problem in advanced chronic kidney disease (ACKD). Motivational interviewing using the stages of change model is an effective combination in promoting behavior modifications. The objective of the present study was to determine the effectiveness of an individual, pre-dialysis intervention program (monthly sessions of 90 min over a 6-month period) in terms of adherence, emotional state and health-related quality of life (HRQL). Forty-two patients were evaluated for adherence, depression, anxiety and HRQL with standardized self-report questionnaires. Biochemical markers were also registered. The results show that after the intervention, patients reported significantly higher levels of adherence, lower depression and anxiety levels, and better HRQL (i.e., general health and emotional role domains). Biochemical parameters were controlled significantly better after the intervention, except for iPTH. These findings highlight the potential benefit of applying individual psycho-educational intervention programs based on motivational interviewing and using the stages of change model to promote adherence and wellbeing in ACKD patients.

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