Carl-Gustaf Elinder

KIDNEY DONORS LIVE LONGER

BACKGROUND A very important issue in living kidney donor transplantation is whether the donation is safe for the donor. The aim of this study was to examine survival and causes of death in kidney donors and to assess the renal function in those who had donated a kidney more than 20 years ago. METHODS A total of 459 living donor nephrectomies were performed in Stockholm from 1964 until the end of 1994. By using national registers, all 430 donors living in Sweden were traced. Donor survival was analysed using the Kaplan-Meier method. Expected survival was computed using the Hakulinens method and was based on national mortality rates. RESULTS Forty-one subjects had died between 15 months and 31 years after the donation. The mortality pattern was similar to that in the general population, the majority dying of cardiovascular diseases and malignancies. After 20 years of follow-up, 85% of the donors were alive, whereas the expected survival rate was 66%. Survival was thus 29% better in the donor group. One third of the donors (aged 46-91 years) who had donated >20 years ago had hypertension. There was a deterioration in the renal function with increasing age, similar to what is seen among normal healthy subjects. The average glomerular filtration rate in donors aged 75 years and over was 48 ml/min/1.73 m2. CONCLUSIONS To donate a kidney does not seem to constitute any long-term risk. The better survival among donors is probably due to the fact that only healthy persons are accepted for living kidney donation.

Low level exposure to cadmium and early kidney damage: the OSCAR study

OBJECTIVES To study the dose-response relation between cadmium dose and renal tubular damage in a population of workers and people environmentally or occupationally exposed to low concentrations of cadmium. METHODS Early kidney damage in 1021 people, occupationally or environmentally exposed to cadmium, was assessed from cadmium in urine to estimate dose, and protein HC (α1-microglobulin) in urine to assess tubular proteinuria. RESULTS There was an age and sex adjusted correlation between cadmium in urine and urinary protein HC. The prevalence of tubular proteinuria ranged from 5% among unexposed people to 50% in the most exposed group. The corresponding prevalence odds ratio was 6.0 (95% confidence interval (95% CI) 1.6 to 22) for the highest exposure group, adjusted for age and sex. Multiple logistic regression analysis showed an increasing prevalence of tubular proteinuria with urinary cadmium as well as with age. After adjustment to the mean age of the study population (53 years), the results show an increased prevalence of 10% tubular proteinuria (taking into account a background prevalence of 5%) at a urinary cadmium concentration of 1.0 nmol/mmol creatinine. CONCLUSION Renal tubular damage due to exposure to cadmium develops at lower levels of cadmium body burden than previously anticipated.

No evidence of accelerated loss of kidney function in living kidney donors : Results from a cross-sectional follow-up

Background. There is a lack of kidneys available for kidney transplantation, and living donors are increasingly used. It is important to examine the possible long-term adverse affect on the renal function and blood pressure of the donors. Methods. We have made a comprehensive follow-up of all living kidney donors at our center from 1964 to 1995. Of 402 donors still alive, we were able to get information about serum creatinine, urinary proteins, and blood cells in urine using reagent strips, and blood pressure from 87%. The glomerular filtration rate (GFR) was estimated using a formula and was measured with Iohexol clearance in 43 of the donors. Individual data on GFR and the prevalence of hypertension were compared with the age- and gender-expected values. Results. The mean age of the examined donors was 61 years (SD:13) at follow-up, and the time since donation was 12 years (SD:8). The average estimated GFR was 72% (SD:18) of the age-predicted value. The ratio of the estimated to the predicted GFR showed no correlation to the time since donation, indicating that there is no accelerated loss of renal function after donation. GFR below 30 ml/min was found in five donors. No donor died in uremia or had dialysis treatment before death. However, three donors developed renal disease, and one was in dialysis treatment. In two of these cases, hereditary factors were possibly involved. Hypertension was present in 38% of the donors but the age-adjusted prevalence of hypertension among donors was not higher than in the general population. Significant proteinuria (≥1.0 g/L) was found in 3% and slight proteinuria (<1.0 g/L) in 9% of the donors. Proteinuria was associated with hypertension and a lower GFR. Conclusions. On average, the remaining renal function of kidney donors did not deteriorate more rapidly than what may be expected from ageing. However one-third of the female and half of the male donors developed hypertension and, approximately, 10% displayed proteinuria. Nevertheless, our study supports the continued use of living kidney donors if strict criteria are used for acceptance.

Low-level cadmium exposure and osteoporosis

Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established. High cadmium exposure causes renal damage and in severe cases also causes osteoporosis and osteomalacia. We have examined whether long‐term low‐level cadmium exposure increases the risk of osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men and 544 women, aged 16–81 years, environmentally or occupationally exposed to cadmium, using dual‐energy X‐ray absorptiometry (DXA) technique. Cadmium in urine was used as the dose estimate and protein HC was used as a marker of renal tubular damage. There was a clear dose‐response relation between cadmium dose and the prevalence of tubular proteinuria. Inverse relations were found between cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over 60 years of age. There was a dose‐response relation between cadmium dose and osteoporosis. The odds ratios (ORs) for men were 2.2 (95% CI, 1.0‐4.8) in the dose group 0.5‐3 nmol Cd/mmol creatinine and 5.3 (2.0‐14) in the highest dose category (≥3 nmol/mmol creatinine) compared with the lowest dose group (<0.5 nmol Cd/mmol creatinine). For women, the OR was 1.8 (0.65‐5.3) in the dose group 0.5‐3 nmol Cd/mmol creatinine. We conclude that exposure to low levels of cadmium is associated with an increased risk of osteoporosis.

Cadmium exposure from smoking cigarettes: Variations with time and country where purchased

Cadmium has been determined in 26 brands of cigarettes purchased in eight different countries throughout the world and in 16 different samples of cigarettes produced in Sweden between 1918 and 1968. In addition the amount of cadmium released from smoking one cigarette to the particulate phase collected from a smoking simulation machine, corresponding to the amount actually inhaled by a smoker, has been determined. The cadmium concentration in different brands of cigarettes ranged from 0.19 to 3.0 micrograms Cd/g dry wt, with a general tendency toward lower values in cigarettes from developing countries. No systematic change in the cadmium concentration of cigarettes with time could be revealed. The amount of cadmium inhaled from smoking one cigarette containing about 1.7 microgram Cd was estimated to be 0.14 to 0.19 microgram, corresponding to about 10% of the total cadmium content in the cigarette.

Cancer mortality of cadmium workers

Several epidemiological studies of workers exposed to cadmium indicate an increased risk of lung and prostatic cancer. The increase is statistically significant in some of the studies but the SMR is greater than 100 in almost all. A cohort study of the mortality among 522 Swedish workers exposed to cadmium for at least one year in a nickel-cadmium battery plant support the earlier findings. The SMR for lung and prostatic cancer increased with increasing dose and latency but did not obtain statistical significance. A combination of all the available data from the most recent follow up of causes of death among cadmium workers in six different cohorts shows 28 cases of prostatic cancer (SMR = 162) and 195 cases of lung cancer (SMR = 121). This new analysis suggests that long term, high level exposure to cadmium is associated with an increased risk of cancer. The role of concomitant exposure to nickel needs further study.

Lead and cadmium levels in blood samples from the general population of Sweden

Lead and cadmium was determined in whole blood samples obtained from 473 nonoccupationally exposed adult persons in Sweden in 1980. Analyses were performed using atomic absorption spectrophotometry equipped with an electrothermal atomization unit. Accuracy of the analysis was confirmed by the analysis of quality control samples. Blood lead concentrations were shown to be significantly influenced by sex, smoking habits, and alcohol consumption. Current male smokers had a median blood lead level of 92 micrograms Pb/liter, as compared to 77 micrograms Pb/liter for nonsmokers. For females the corresponding values were 69 micrograms Pb/liter and 57 micrograms Pb/liter for current smokers and nonsmokers, respectively. Highly significant correlations were found between stated alcohol consumption and blood lead in most of the different sex and smoking categories. People living in apartments close to streets with heavy traffic in Stockholm had slightly, but not significantly, higher blood lead levels when compared to people living in areas of this city with low traffic density. Blood cadmium levels were very strongly affected by smoking habits. A significant correlation existed between the number of cigarettes consumed daily and blood cadmium concentration. The median blood cadmium level for nonsmoking males was 0.2 micrograms Cd/liter (less than or equal to 0.2, detection limit) and for females 0.3 micrograms Cd/liter. About 90% of all nonsmokers had cadmium concentrations in blood below 0.6 micrograms Cd/liter, whereas about 90% of the current male and female smokers had cadmium concentrations in blood of 0.6 micrograms Cd/liter or more.

Decreased Kidney Function Among Agricultural Workers in El Salvador

BACKGROUND An epidemic of chronic kidney disease of unknown cause has emerged along the Pacific coast of Central America, particularly in relatively young male sugarcane workers. In El Salvador, we examined residence and occupations at different altitudes as surrogate risk factors for heat stress. STUDY DESIGN Cross-sectional population-based survey. SETTING & PARTICIPANTS Populations aged 20-60 years of 5 communities in El Salvador, 256 men and 408 women (participation, 73%): 2 coastal communities with current sugarcane and past cotton production and 3 communities above 500 m with sugarcane, coffee, and service-oriented economies. PREDICTOR Participant sex, age, residence, occupation, agricultural history by crop and altitude, and traditional risk factors for CKD. OUTCOMES Serum creatinine (SCr) level greater than the normal laboratory range for sex, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and proteinuria categorized as low (protein excretion ≥ 30-< 300 mg/dL) and high grade (≥ 300 mg/dL). RESULTS Of the men in the coastal communities, 30% had elevated SCr levels and 18% had eGFR < 60 mL/min/1.73 m2 compared with 4% and 1%, respectively, in the communities above 500 m. For agricultural workers, prevalences of elevated SCr levels and eGFR < 60 mL/min/1.73 m2 were highest for coastal sugarcane and cotton plantation workers, but were not increased in sugarcane workers at 500 m or subsistence farmers. Women followed a weaker but similar pattern. Proteinuria was infrequent, of low grade, and not different among communities, occupations, or sexes. The adjusted ORs of decreased kidney function for 10-year increments of coastal sugarcane or cotton plantation work were 3.1 (95% CI, 2.0-5.0) in men and 2.3 (95% CI, 1.4-3.7) in women. LIMITATIONS The cross-sectional nature of the study limits etiologic interpretations. CONCLUSION Agricultural work on lowland sugarcane and cotton plantations was associated with decreased kidney function in men and women, possibly related to strenuous work in hot environments with repeated volume depletion.

Association between Smoking and Chronic Renal Failure in a Nationwide Population-Based Case-Control Study

For determining whether smoking is associated with an increased risk for chronic renal failure (CRF) overall and by type of renal disease, smoking data were analyzed from a nationwide population-based case-control study. Eligible as cases were native 18- to 74-yr-old Swedes whose serum creatinine for the first time and permanently exceeded 3.4 mg/dl (men) or 2.8 mg/dl (women). A total of 926 cases (78% of all eligible) and 998 control subjects (75% of 1330 randomly selected subjects from the source population), frequency matched to the cases by gender and age within 10 yr, were included. A face-to-face interview and a self-administered questionnaire provided information about smoking habits and other lifestyle factors. Logistic regression models estimated odds ratios (OR) as measures of relative risk for disease-specific types of CRF among smokers compared with never-smokers. Despite a modest and nonsignificant overall association, the risk increased with high daily doses (OR among smokers of >20 cigarettes/d, 1.51; 95% confidence interval [CI], 1.06 to 2.15), long duration (OR among smokers for >40 yr, 1.45; 95% CI, 1.00 to 2.09), and a high cumulative dose (OR among smokers with >30 pack-years, 1.52; 95% CI, 1.08 to 2.14). Smoking increased risk most strongly for CRF classified as nephrosclerosis (OR among smokers with >20 pack-years, 2.2; 95% CI, 1.3 to 3.8), but significant positive associations were also noted with glomerulonephritis. This study thus suggests that heavy cigarette smoking increases the risk of CRF for both men and women, at least CRF classified as nephrosclerosis and glomerulonephritis.

Cadmium and Lead in Blood in Relation to Low Bone Mineral Density and Tubular Proteinuria

Long-term exposure to cadmium may cause kidney and bone damage. Urinary cadmium is commonly used as the dose estimate for the body burden of cadmium. However, elevated levels of cadmium in the urine may reflect not only high levels of cadmium dose but also renal dysfunction. In this study we used blood cadmium as the dose estimate. In addition, we analyzed blood lead. We examined 479 men and 542 women, ages 16-81 years, who were environmentally or occupationally exposed to cadmium and lead. We used urinary protein alpha 1-microglobulin as a marker for tubular proteinuria and measured forearm bone mineral density using dual-energy X-ray absorptiometry. The relationship between blood cadmium and tubular proteinuria was strong, even when we excluded occupationally exposed participants. The subgroup with the highest blood cadmium levels had a 4-fold risk of tubular proteinuria compared to the subgroup with the lowest blood cadmium levels. In the older age group (age > 60), the risk of low bone mineral density (z-score < -1) for the subgroup with the highest blood cadmium levels was almost 3-fold compared to the group with lowest blood cadmium levels. We found no similar associations for lead. The observed effects may be caused by higher cadmium exposure in the past. This study strengthens previous evidence that cadmium exposure may affect both bone mineral density and kidney function.