KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

Bone metabolism and disease in chronic kidney disease

Background Elevated calcium and phosphorus levels after therapy with injectable vitamin D for secondary hyperparathyroidism may accelerate vascular disease and hasten death in patients undergoing long-term hemodialysis. Paricalcitol, a new vitamin D analogue, appears to lessen the elevations in serum calcium and phosphorus levels, as compared with calcitriol, the standard form of injectable vitamin D. Methods We conducted a historical cohort study to compare the 36-month survival rate among patients undergoing long-term hemodialysis who started to receive treatment with paricalcitol (29,021 patients) or calcitriol (38,378 patients) between 1999 and 2001. Crude and adjusted survival rates were calculated and stratified analyses were performed. A subgroup of 16,483 patients who switched regimens was also evaluated. Results The mortality rate among patients receiving paricalcitol was 3417 per 19,031 person-years (0.180 per person-year), as compared with 6805 per 30,471 person-years (0.223 per person-year) am...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa022536

Survival of Patients Undergoing Hemodialysis with Paricalcitol or Calcitriol Therapy

Renal osteodystrophy

https://www.kidney-international.org/article/S0085-2538(15)49271-3/pdf

A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients.

Background. Adynamic bone disease was recently described to be increasingly prevalent in the dialysis population. At present the diagnosis of this type of renal osteodystrophy can only be made by bone histomorphometry. We assessed the value of different biochemical serum markers in the diagnosis of adynamic bone disease. Methods. In 103 haemodialysis patients a bone biopsy was performed after double tetracycline labelling, and the serum levels of intact PTH, osteocalcin, and the bone isoenzyme of alkaline phosphatase were determined. Bone alkaline phosphatase was measured by an optimized agarose gel electrophoretic method, recently shown to have a high accuracy, precision and reproducibility, also in the lower range. Results. In 38 (37%) of the patients the diagnosis of adynamic bone disease was histologically established. Constructing receiver operator curves optimal cut-off levels for the diagnosis of adynamic bone disease were determined, being ≤27 U/litre for the bone isoenzyme of alkaline phosphatase, ≤14 μg/litre for osteocalcin and ≤150 pg/ml for intact PTH. Concentrations of bone alkaline phosphatase or intact PTH below these cut-off levels, were shown to be the best performing tests in the detection of adynamic bone disease as indicated by a sensitivity of 78.1 and 80.6% and a specificity of 86.4 and 76.2% respectively. Applying Bayes' theorema, it was calculated that in the current haemodialysis population in which a prevalence of adynamic bone disease up to 35% has been described, the positive predictive values for the proposed cut-off values are 75% for bone alkaline phosphatase, 65% for intact PTH and 55% for osteocalcin. Moreover, in this population, levels of bone alkaline phosphatase and intact PTH below the optimal cut-off excluded hyperparathyroid bone disease. Conclusion. In view of the relative easy and accurate methodology for bone alkaline phosphatase determination, the closer physiological link with osteoblast function and the lesser expense for its determination we suggest that this marker is a useful tool in the noninvasive diagnosis of the adynamic type of bone disease in the individual patient.

/pdf/low-serum-levels-of-alkaline-phosphatase-of-bone-origin-a-4cu8tt3sql.pdf

Low serum levels of alkaline phosphatase of bone origin: a good marker of adynamic bone disease in haemodialysis patients

Background. Aiming at a safe method in the diagnosis of aluminium-related bone disease (ARBD)/aluminium overload the low-dose desferrioxamine (DFO) test was developed. In a multicentre study histological and histochemical data and aluminium bulk analysis of bone biopsies of 77 dialysis patients were correlated with the results of both the 5 mg/kg and 10 mg/kg DFO tests. Methods. ARBD was considered to be present when >15% of the bone surface was positively stained for aluminium and the bone formation rate was below 220 μm 2 /mm 2 /day. Patients in which the Aluminon® staining was positive (>0%) were considered at an increased risk for aluminium toxicity independent of the type of renal osteodystrophy. Patients were considered aluminium overloaded when the bone aluminium content was >15 μg/g wet weight and/or the Aluminon® staining was positive (>0%). Results. Using the proposed criteria 15 patients were found to have ARBD ; 13 of them presenting with a serum iPTH below 150 ng/l. In conjunction with an iPTH measurement the DFO test had a more than acceptable sensitivity and specificity in the diagnosis of ARBD. The test was considered positive when a post-DFO serum aluminium increment (ΔsAl) above 50 μg/l (5 mg/kg) or 70 μg/l (10 mg/kg) together with a serum iPTH below 150 ng/l was found. Using these cut-off levels the 5 and 10 mg/kg tests in the diagnosis of ARBD had a sensitivity of 87% and a specificity of 95% and 92% respectively whereas the predictive value for a positive test for the population under study was 80% (5 mg/kg). Not a single patient with a serum iPTH >650 ng/l had a positive staining (>0%) even when the bone aluminium level was elevated (> 15 μg/g wet weight). In the detection of patients at risk for aluminium toxicity ΔsAl thresholds of 50 μg/l (5 mg/kg) and 70 μg/l (10 mg/kg) in combination with a serum iPTH < 650 ng/l had a sensitivity of 92% and specificity of 86% and 84% respectively. In the clinical setting of aluminium overload, threshold ΔsAl levels of 50 μg/l (5 mg/kg) and 70 μg/l (10 mg/kg) had a sensitivity of 91% and a specificity of 95% and 90% respectively. Conclusions. The low-dose DFO test is a reliable test for the detection of aluminium overload ; however, it is not specific enough to differentiate between ARBD, increased risk of aluminium toxicity, and aluminium overload unless it is used in combination with a serum iPTH measurement. In conjunction with a serum iPTH measurement it is an important tool in the differential diagnosis and may avoid the necessity of a bone biopsy in the majority of patients. Data obtained in the present study have allowed us to update the strategies for monitoring, diagnosis and patient follow-up proposed at the Consensus Conference on Diagnosis and Treatment of Aluminium Overload in End-Stage Renal Failure ; Paris, 1992.

Use of the low-dose desferrioxamine test to diagnose and differentiate between patients with aluminium-related bone disease, increased risk for aluminium toxicity, or aluminium overload

We studied the removal of aluminoxamine (AlO) and ferrioxamine (FO) by (i) hemoperfusion/hemodialysis using an AluKart in combination with either a Cuprophan F-120 or a Hemophan FH-160 membrane, or (ii) hemodialysis with a high-flux F-60 polysulfone membrane. The same six dialysis patients underwent in a random order dialysis by the three set-ups after i.v. infusion of 30 mg/kg of desferrioxamine (DFO) during the last half an hour of the preceding dialysis session. The mean +/- SD plasma AlO and FO clearances of the AluKart combined with either a F-120 or FH-160 membrane were 194.3 +/- 25.8 ml/min (AlO) and 164.2 +/- 41.3 ml (FO) at the start of dialysis declining to respectively 76.6 +/- 27.3 and 68.5 +/- 42.6 ml/min at the end of dialysis. With a high-flux dialysis membrane the intra-dialytic plasma clearance remained constant at 81.5 +/- 6.8 ml/min for AlO and 60.0 +/- 2.8 ml/min for FO. In the presence of an AluKart combined with a FH-160 up to 84 +/- 27% and 84 +/- 19% of the available AlO and FO could be removed during a four-hour hemoperfusion/hemodialysis session. During the first hour of dialysis, respectively 59 and 58% of the total amount of AlO and FO extracted by the AluKart was removed compared to only 9 and 16% during the last hour.(ABSTRACT TRUNCATED AT 250 WORDS)

E. Lemoniatou

Papers

Low serum levels of alkaline phosphatase of bone origin: a good marker of adynamic bone disease in haemodialysis patients

Use of the low-dose desferrioxamine test to diagnose and differentiate between patients with aluminium-related bone disease, increased risk for aluminium toxicity, or aluminium overload

Removal of aluminoxamine and ferrioxamine by charcoal hemoperfusion and hemodialysis using different types of dialysis membranes