The results of our screening examination indicate that in a proportion of long-term lithium-treated patients, the markers of kidney damage can be detected. They include increased serum creatinine levels, glomerular filtration rate reduced below 60 ml/min/1.73 m2, and increased urinary albumin excretion. These results confirm those of other studies and meta-analyses. Generally, the percentages of patients showing particular abnormalities are similar to those described in the recent literature.
The mean value of serum creatinine level in our group of patients (1.0 mg/dl =88 μmol/l) was similar to that McCann et al. [16
] (85 μmol/l) obtained in 59 patients, with mean age of 55 years, and using lithium for a mean of 9.5 years. The authors demonstrated a positive association between duration of lithium use and serum creatinine levels; this association was found at the level of statistical trend (p<0.1) only in male patients,.
Calculated GFR values are considered to be better indicators of kidney function than are Scr values [14
]. The mean value of eGFR in our study was similar to the GFR value reported by Tredget et al. [10
] in their group of 61 patients using lithium for a mean of 15.6 years (70 vs.
66 ml/min/1.73 m2
, respectively). The percentage of patients showing eGFR <60 ml/min/1.73 m2
in our patients was slightly lower than in their study (23% vs.
34.4%, respectively), but it was similar to their’s in our subgroup of male patients. Tredget et al. [10
] did not compare GFR in men and women.
In our study, eGFR values negatively correlated with age in men, but not in women. It was established that GFR values decline with increasing age in the general population . It is also known that male sex is a risk factor for progression of kidney function impairment. Therefore, it seems reasonable to assume that men are more susceptible than women to kidney injury associated with long-term lithium therapy. However, a significant association between the duration of lithium treatment and eGFR in men was not demonstrated in our cross-sectional screening study. This assumption is in agreement with the results of a recent study by Bendz et al. [11
], performed in 3369 lithium-treated Swedish patients. The authors revealed that end-stage chronic kidney disease associated with long-term lithium therapy developed in about 1.2% of patients, mostly men [11
The increase of albuminuria expressed as urinary albumin/creatinine ratio (UACR), mainly in the microalbuminuric range, was found in 16% of our patients. Danish investigators found a significant elevation of urinary albumin excretion in lithium-treated patients compared to control subjects [17
], but they did not estimate the percentage of lithium-treated patients who had abnormal albuminuria. In our study, increased albuminuria was found twice as frequently in men than in women. It is known that increased albuminuria is an early marker of kidney damage [14
An unexpected finding in our study was the fairly high percentage (19%) of patients with high serum albumin (>52 g/l). In female patients, Salb significantly correlated with lithium level. Hyperalbuminemia is mainly associated with dehydration [14
], but our patients did not show other signs of dehydration. It may be speculated that in lithium-treated patients demonstrating hyperalbuminemia, an impaired urine concentrating ability caused polyuria, which was not adequately corrected by increased fluid intake, and resulted in hemo-concentration. In 16% of our patients the specific gravity of the random urine sample was <1.005, suggesting polyuria, but serum albumin concentration did not correlate with the specific gravity of the random urine sample (r=0.09, NS). The tendency to hyperalbuminemia in long-term lithium-treated patients has not yet been reported and needs further observation.
There have been few studies on the markers of kidney damage during long-term lithium administration in relation to sex.
The results of the present study indicate that male patients may be more vulnerable to a possible renal impairment connected with long-term lithium therapy. Therefore, while systematic monitoring of lithium function in all patients taking lithium for 10 years should be mandatory, male patients should be the subject of special attention in this respect.