Increased end-stage diabetic nephropathy in Indo-Asian immigrants living in the Netherlands.

AIMS/HYPOTHESIS: We aimed to investigate the risk of end-stage diabetic nephropathy due to Type II (non-insulin-dependent) diabetes mellitus in Indo-Asian immigrants from Surinam. METHODS: A demographically based case-control study was carried out in Surinamese Indo-Asian immigrants and Dutch Caucasian subjects. All patients with end-stage diabetic nephropathy who had started dialysis between 1990 and 1998 were identified through a national registry of all patients entering a renal replacement program in the Netherlands. The general population of native Dutch and Surinamese Indo-Asians were considered the control subjects. RESULTS: Among Indo-Asian immigrants, the age adjusted relative risk of end-stage diabetic nephropathy was 38 (95 % CI 16 to 91) compared with the native Dutch population. The duration of diabetes until the start of dialysis treatment was similar in both ethnic groups, about 17 years. CONCLUSION/INTERPRETATION: The Indo-Asian subjects had a nearly 40-fold increase in the risk for end-stage diabetic nephropathy due to Type II diabetes, compared with the native Dutch population. This was higher than expected on the basis of the eightfold higher prevalence of diabetes in the Indo-Asian population. The similar duration of diabetes until the start of dialysis treatment in both ethnic groups supports the hypothesis of a higher incidence of diabetic nephropathy in the Indo-Asian diabetic population. Early and frequent screening for diabetes and microalbuminuria is recommended in Indo-Asian subjects.

Nature's high-voltage injuries: sometimes a deadly consequence.

A patient is described who presented with the clinical picture of respiratory failure, persistent comatose state and myocardial injury after being struck by lightning. The discussion reviews the management of lightning injuries with emphasis on cardiovascular and neurological complications.

H reflexes as a measure for uremic polyneuropathy. A longitudinal study in patients treated with dialysis or renal transplantation.

Assessment of peripheral nerve function in end stage uremia by clinical and conventional nerve conduction velocity studies was compared to that using H reflex measurements. The latter proved to be the most sensitive technique. The results of the test correlated well with clinical and with other neuro-physiological measures. Nerve function as evaluated by H reflexes remained stable during the first 2 years of dialysis, but deteriorated later on. H reflex latencies shortened after renal transplantation. The results of H reflex measurements did not correlate with biochemical parameters, which makes the test a less attractive overall measure for the efficiency of therapy in uremia. In the follow-up of patients under treatment for uremic polyneuropathy, however, recording of H reflexes provides an important measure.

Influence of ageing on antibody formation in vivo after immunisation with the primary T-cell dependent antigen Helix pomatia haemocyanin.

The in vivo antibody response to the primary T-cell dependent antigen Helix pomatia Haemocyanin (HPH) was studied, in order to detect the possible presence of a humoral immune deficiency in ageing. The IgG subclass distribution of the specific antibodies was also determined. In order to define a dose of HPH which could be used to discriminate between the responsiveness of healthy and immunocompromised individuals, we first established a dose-response curve for this antigen in 60 healthy young volunteers. Their responses were compared with the responses of a group of patients suffering from end stage renal failure. The patients who were treated with haemodialysis showed a significantly lower IgM, IgG and IgA anti-HPH antibody response after immunisation with a dose of 30 micrograms HPH, which could be restored by increasing the antigen dose. Patients treated with continuous ambulant peritoneal dialysis and a group of elderly persons, selected according to the Senieur protocol, showed no impairment of antibody formation after immunisation with 30 micrograms HPH, but in the non-Senieur elderly the anti-HPH antibody response was significantly lower. Furthermore, Senieur and non-Senieur elderly persons showed a diminished IgG2 anti-HPH antibody formation, whereas in the elderly non-Senieur individuals and in the patients with renal insufficiency, IgG1 and IgG3 anti-HPH antibodies were also diminished. This study clearly shows that the so-called age-associated immune deficiency can be the result of disease and is not necessarily due to the ageing process itself.

Encephalopathy in patients on continuous ambulatory peritoneal dialysis and patients on chronic haemodialysis.

A group of 121 patients, 22 with a preterminal chronic renal insufficiency (PCRI), 74 on chronic haemodialysis (CHD), and 25 on continuous ambulatory peritoneal dialysis (CAPD), was evaluated by means of neurophysiological and neuropsychological studies to detect signs of central nervous system dysfunction. CHD patients were studied the day before dialysis treatment. In each patient the neurophysiological and neuropsychological studies were performed on the same day. The same overall result emerged from the neurophysiological and neuropsychological studies: all three patient groups showed significant deviations from the values obtained from a healthy reference group, whereas no differences were found between the three patient groups. Biochemical variables (a.o. PTH, Al, PO4) showed inconsistent or only minor correlations with the encephalopathic parameters. Apparently traditional biochemical variables are not a reliable measure to safeguard renal patients from neurotoxic damage. With respect to central nervous system dysfunction CAPD appears to be as 'safe' as CHD.

The role of 1,25-dihydroxyvitamin D in the maintenance of hypercalcemia in a patient with an ovarian carcinoma producing parathyroid hormone-related protein.

The syndrome of humoral hypercalcemia of malignancy (HHM) is thought to be mainly a result of the production of parathyroid hormone-related protein (PTHRP) by malignant tumors. Serum 1,25-dihydroxyvitamin D (1,25-DHD) concentrations are generally low in such patients, which contrasts with the findings in animal studies. A patient is reported with HHM from a clear cell ovarian carcinoma and elevated serum immunoreactive PTHRP (about five times the upper limit of normal) in whom serum 1,25-DHD concentrations were abnormally high (200 pmol/l) and associated with increased intestinal calcium absorption. Treatment with two different nitrogen-containing bisphosphonates (pamidronate and [3-dimethyl-amino-1-hydroxypropylidene]-1,1-bisphosphonate) did not normalize serum and urinary calcium despite effective inhibition of bone resorption. These observations suggested an additional intestinal contribution to the maintenance of hypercalcemia. Tumor removal was followed by decreases in serum immunoreactive PTHRP and 1,25-DHD concentrations to their respective normal ranges and normocalcemia. Separating HHM into Types I and II, according to the prevailing serum 1,25-DHD concentrations, can provide a basis for a better understanding of the pathogenesis of hypercalcemia, and it also may have practical use in the successful management of these patients.

Ketanserin pharmacokinetics in patients with renal failure.

1. The pharmacokinetics of ketanserin and its major metabolite ketanserin-ol were investigated after a single oral dose of 40 mg and after chronic oral administration of 20 or 40 mg twice daily for 10 days in 12 patients with chronic renal insufficiency of whom six were on intermittent haemodialysis. Plasma protein binding of ketanserin was measured in these 12 patients and in eight healthy volunteers. 2. In both dialysis and non-dialysis patients the terminal half-life of ketanserin (mean +/- s.d.) was prolonged compared with that reported previously for healthy volunteers (28 +/- 4 h vs 18 +/- 4 h). This may be explained by a lowered renal clearance of ketanserin-ol from which ketanserin is partly regenerated. 3. In patients with chronic renal insufficiency plasma ketanserin concentrations were similar to those found in healthy subjects after the same dose. Plasma ketanserin-ol concentrations were elevated, resulting in a raised AUC ratio of ketanserin-ol to ketanserin as compared with healthy individuals (7.3 +/- 4.0 vs 3.2 +/- 0.7). 4. Urinary excretion of ketanserin was negligible in both dialysis and non-dialysis patients, and ketanserin-ol excretion was markedly lowered. 5. The plasma protein binding of ketanserin was slightly reduced in comparison with healthy volunteers (93.7 +/- 1.0% vs 95.0 +/- 0.2%). 6. A dose regimen of 20 mg twice daily appeared to be well tolerated in spite of less plasma binding in renal failure.