James Heaf

Causes and Consequences of Adynamic Bone Disease

Adynamic bone disease (ABD), a.k.a. aplastic lesion, is a histological condition found in uremic patients. It is characterized by low bone resorption and formation, and, in contrast to osteomalacia, the amount of osteoid tissue is normal or low. The condition was first described in the 1980s and was primarily ascribed to aluminum bone intoxication [1–3]. Even at the height of the aluminum epidemic, it was however clear that not all cases could be related to aluminum [4]. During the 1990s, aluminum hydroxide phosphate binders were replaced, mainly by calcium carbonate and calcium acetate. While this has resulted in the virtual disappearance of aluminum bone disease, the incidence of ABD has, if anything, increased [5], and most cases are clearly unrelated to aluminum [5– 8]. However, while the aluminum-related form of the disease is associated with substantial morbidity in the form of bone pain and increased fracture incidence [9], the nonaluminum form is generally asymptomatic [10, 11] and it is controversial whether it causes increased morbidity (fig. 1).

Reliability testing of the Danish version of the Kidney Disease Quality of Life Short Form

Objective. The questionnaire Kidney Disease Quality of Life Short Form version 1.3 (KDQOL-SF™) is valuable for assessing the health-related quality of life in patients treated with chronic dialysis. The aim of this study was to translate and test the reliability of the KDQOL-SF for use in Denmark. Material and methods. Translation into Danish and back-translation into English were performed. Pilot, field and internal consistency reliability tests were performed. Results. Cronbachs α coefficients for the internal reliability test ranged from 0.77 to 0.93 for the eight generic scales. In a test involving all patients, two of the disease-specific scales had Cronbachs α coefficients of <0.70 (“social support”u200a=u200a0.67; and “quality of social interaction”u200a=u200a0.43). After removing one item from the scale “quality of social interaction”, Cronbachs α reached 0.63. A test of the scores of peritoneal dialysis (PD) patients discovered low reliability for three disease-specific scales. The KDQOL-SF manual and the Danish manual for the Short Form 36 (SF36) differed in the scoring of four generic scales: “role limitation—physical”, “bodily pain”, “general health” and “social function”. Conclusions. With the exception of the scale “quality of social interaction” the Danish translation of the KDQOL-SF achieved values in the internal consistency reliability test of the same level as the original U.S. version. When data were stratified according to dialysis treatment, the reliability of PD patients scores was lower. Generic data from the questionnaire SF36 should be scored according to the Danish SF36 manual.

Normalised cellular clearance of creatinine, urea and phosphate.

The observation of a significant postdialysis rebound in the serum concentration of small molecules demonstrates the existence of a limited cellular clearance (KC). Theory suggests that KC is proportionate to weight, and it is therefore more rational in interindividual comparisons to measure the normalised cellular clearance (KCn). Both variables can be determined from the shape of the rebound curve. KC and KCn were determined in 34 maintenance dialysis patients on two occasions, obtaining the following values: KC urea 502 +/- 179 ml/min, KCn urea 7.80 +/- 2.42 ml/kg/min, KC creatinine 394 +/- 141 ml/min, KCn creatinine 6.03 +/- 1.42 ml/kg/min, KC phosphate 369 +/- 132 ml/min, KCn phosphate 5.62 +/- 1.24 ml/kg/min. KC was significantly correlated to weight for all three substances, but no correlation was seen between KCn and weight, height, age, sex, uremia duration or dialysis duration. KCn urea was significantly higher that KCn creatinine and KCn phosphate. KC urea was substantially lower than previously published figures, suggesting that some dialysis patients may be underdialysed due to overestimation of KT/V using conventional single-compartment urea kinetic modelling.

The Reliability and Representativity of Non-Dynamic Bone Histomorphometry in Uremic Osteodystrophy

In order to evaluate the reliability and representativity of iliac crest bone biopsy in uremic osteodystrophy, non-dynamic bone histomorphometry was performed post-mortem on the right and left iliac crests and the 3rd lumbar vertebra in 20 patients with chronic uremia. High (> 0.8) right-left correlation coefficients were found for bone volume, osteoid volume, osteoid surface, osteoid thickness, eroded surface, osteoclast surface and aluminium labelling intensity; moderate (0.7-0.8) for trabecular thickness, and low (< 0.7) for cortical thickness, porosity and aluminium bone concentration. High iliac crest-vertebra correlations were found for trabecular thickness, osteoid volume, osteoid surface, eroded surface, osteoclast surface and aluminium labelling intensity, and low correlations for bone volume, osteoid thickness and bone aluminium concentration. In conclusion, non-dynamic iliac trabecular bone indices are reliable variables and, with the possible exception of bone mass determination, indicative of systemic bone disease. Bone aluminium concentration and cortical bone indices are unreliable measures of uremic bone disease. These reservations apply to the diagnostic use of biopsy in individuals, but not necessarily its research use in groups of patients.

Increased technetium‐99 m hydroxy diphosphonate soft tissue uptake on bone scintigraphy in chronic kidney disease patients with secondary hyperparathyroidism: correlation with hyperphosphataemia

In bone scan patients with dialysis‐treated chronic kidney disease (CKD) and hyperparathyroidism, soft tissue accumulation of technetium‐99 m hydroxy/methylene diphosphonate (Tc‐99 m‐HDP/MDP) has been reported primarily in case reports and usually explained by hypercalcaemia and/or hyperphosphataemia. As human vascular smooth muscle cells produce hydroxyapatite during cell culture with increased phosphate levels and as Tc‐99 m‐HDP/MDP primarily binds to hydroxyapatite, we hypothesized that soft tissue accumulation would be found in patients with hyperphosphataemia. We identified 63 CKD patients diagnosed with secondary hyperparathyroidism admitted for Tc‐99 m‐HDP bone scan. Baseline characteristics and mean concentrations of biochemical markers (including P‐calcium and P‐phosphate) taken 0–3 months prior to the bone scans were collected. Soft tissue uptake was detected on bone scans in 37 of 63 (59%) patients. Primary locations were in the heart (27/37 = 73%), muscles (12/37 = 32%), lung (9/37 = 24%) and gastrointestinal tract (6/37 = 16%), and 13 of 37 (35%) patients had simultaneous uptake in more than one location. Regarding biochemical markers, patients with soft tissue uptake only differed from patients without in terms of plasma phosphate levels (1·95 ± 0·15 (n = 37) versus 1·27 ± 0·08 (n = 26), P = 0·0012). All patients with myocardial uptake (n = 27) had a coronary arteriography‐verified history of coronary artery disease (CAD), whereas CAD was only present in six of the 36 patients without myocardial uptake. In conclusion, dialysis‐treated CKD patients with secondary hyperparathyroidism have a high incidence of soft tissue uptake, and this finding is strongly correlated with elevated phosphate, but not calcium values.

Mesangioproliferative glomerulonephritis: a 30-year prognosis study

Background: Diffuse mesangioproliferative glomerulonephritis (MesP) is the most commonly diagnosed type of glomerulonephritis (GN) in Denmark, with an incidence of 10.8 million per year. In the present study, the 30-year renal survival was estimated. Methods: A retrospective cohort investigation of 140 patients with biopsy-proven MesP was performed between the period 1967-2006. Factors influencing renal survival were investigated using Cox regression analysis. Results: Renal survival at 5, 10, 20 and 30 years was 87, 78, 59 and 50%, respectively. Female survival after 30 years was significantly better than male survival (70 vs. 40%, p = 0.049). Multivariate analysis, adjusted for age, estimated glomerular filtration rate (GFR) and nephrotic syndrome (NS) was performed for each sex individually. An increase in GFR was associated with a hazard risk (HR) of 0.98 (p = 0.02) in women and 0.99 (p = 0.006) in men. Older age was associated with a HR of 1.04 (p = 0.02) in women and 1.03 (p = 0.004) in men. NS had a poorer prognosis in men (HR 2.53, p = 0.01), but not in women (HR 0.54, p = 0.38). Conclusion: Increasing age and decreasing GFR were adversely associated with renal death. Renal prognosis was better for women after 30 years, and NS resulted in a poorer prognosis in men. This suggests that disease course and prognosis are different between men and women.