[Denosumab and fracture risk in kidney transplant].

Background: Kidney transplant patients bear a higher risk of bone disease. The monoclonal antibody Denosumab (Den), by binding RANKL, reduces osteoclastic activity and increases mineral density (BMD), thus limiting the risk of bone fractures. We evaluated the efficacy and safety of Den in kidney transplant patients who developed bone fractures. Methods: Thirteen kidney transplant recipients (aged from 50 to 79 years 7M and 6F, with an average 9,9 years follow up after transplantation, and nearly normal renal function (GFR 62±15 ml/min/1.73m2), who developed low-energy vertebral fractures (21 dorsal and 1 lumbar) after transplantation, had been evaluated for 2 years with Dual-energy X-ray absorptiometry (DEXA) and morphometric absorptiometry (MXA) while receiving Den (four 60-mg doses). Data for vertebral heights and posterior-anterior height ratios (P/A), and BMD values for vertebral, femoral, and radius were obtained. The immunosuppressive regimen consisted of CNI and MMF, and 8 out of 13 were taking prednisone. A fixed dose of 450.000 UI-year of cholecalciferol was prescribed to all patients. Whole-PTH, 25-OHD3, and alkaline phosphatase (ALP) were also evaluated. Results: After 2 years of Den treatment, we observed a significative increase in vertebral T-score (from -2.12±0.35 to -1.67±0.35; p < 0.02), while T score of femoral neck and radius did not show significative variation (-1.86±0.21 versus -1.84±0.23 and -3.04±0.42 versus -3.19±0.45, respectively). We found a lower incidence of fracture/patient-year pre and post Den 0.17 [95 CI 0.11-0.24] vs 0.07 [95% CI 0.02-0.3] respectively. No significative variations were observed in whole-PTH (89.31±19.9 pg/ml versus 68.38±9.8 pg/ml), 25OHD3 (24.02±2.75ug/L versus 26.67±2.29 ug/L) and alkaline phosphatase (78.46±12.73UI/L versus 56.77±7.14UI/L). No adverse events were registered. Conclusions: Treatment with Den improve BMD in vertebral bone and possibly reduces the risk of low-energy vertebral fractures in kidney transplant patients.

Rosuvastatin-induced acute interstitial nephritis.

We report a case of acute interstitial nephritis (AIN), most likely induced by rosuvastatin, in an 83-year-old male patient. The patient underwent angioplasty of the left internal carotid artery, after which he began a regimen of rosuvastatin (20 mg/day). After 3 weeks the patient was admitted to our unit for acute renal failure with mild proteinuria with negligible urinary sediment. A left kidney biopsy showed dense interstitial infiltrates, mainly composed of lymphocytes with evident tubulitis. Rosuvastatin withdrawal plus prednisolone (1 mg/kg/day) treatment, which was slowly tapered over a period of 4 weeks, allowed for a complete recovery of renal function. To our knowledge, this is the first case report of rosuvastatin-induced AIN. Acute renal failure is associated with a clear increase in morbidity, length of hospital stay and mortality. Moreover, since statins are among the most widely prescribed drugs in Western countries, we think that the risk of AIN should be taken into account as a possible side effect of rosuvastatin.

Lanthanum carbonate: a postmarketing observational study of efficacy and safety.

BACKGROUND: Hyperphosphatemia is associated with morbidity and mortality in hemodialysis patients. The use of calcium chelators is restricted by the risk of hypercalcemia and vascular calcifications. Sevelamer, a non-calcium chelator, is associated with risks of metabolic acidosis and poor compliance. Lanthanum carbonate is a non-calcium chelator not associated with these issues. However, accumulation in liver and bone has been a reason for concern. METHODS: Adult patients (n=112) from 9 hemodialysis centers, with serum phosphorus >5.5 mg/dL and on hemodialysis for >1 year, were selected to switch to lanthanum carbonate (mean dosage: 2,189 ± 491 mg/day); 103 completed the study. Laboratory assays for serum phosphate, calcium, parathyroid hormone, alkaline phosphatase, gamma-glutamyl transpeptidase (gammaGT), aspartate transaminase, alanine transaminase and plasma bicarbonate were performed monthly. Seven patients underwent a bone biopsy for evaluation of lanthanum bone content. RESULTS: Switching to lanthanum carbonate led to a reduction in mean serum phosphate levels (-18.2%; p<0.001) and calcium × phosphorus product (-17.6%; p<0.0001). There were no important changes in other variables, except for an increase in transaminases in 2 patients with preexisting liver disease, who discontinued therapy. An increase in plasma bicarbonate concentration was observed (p=0.001). Although some lanthanum was detected in bone, its distribution did not follow the mineralization front. CONCLUSIONS: Lanthanum carbonate is effective and well tolerated, provided that recipients do not have preexisting liver disease. After 8 months of treatment, lanthanum was not detected in the mineralization front of bone. In hemodialysis patients, lanthanum carbonate does not seem to be involved in metabolic bone disease.

Dose individualization can minimize nephrotoxicity due to carboplatin therapy in patients with ovarian cancer.

Carboplatin (Carbo-Pt), an alkylating agent cleared from the plasma through glomerular filtration, is commonly used for the treatment of ovarian cancer. When administered at high dosage or to patients with reduced renal function, Carbo-Pt may be nephrotoxic. The dose of Carbo-Pt is calculated with Calvert formula, using the value of 24-hour creatinine clearance (24h Ccr) as an estimate of glomerular filtration rate (GFR). The aim of this study was to evaluate the possibility of individualizing the dose of Carbo-Pt using an alternative method to estimate GFR, based on body composition analysis, and then to assess the nephrotoxicity of Carbo-Pt therapy individualized with this new method. First, we evaluated the agreement between GFR (renal clearance of diethylene triamine pentaacetic acid (99mTc-DTPA)), 24h Ccr, and the new estimate of GFR (BCMGFR) calculated on the basis of individual values of body cell mass (BCM) and plasma creatinine. BCMGFR gave a better estimate of GFR than 24h Ccr. Then, we evaluated the nephrotoxicity of a combination chemotherapy based on Carbo-Pt (AUC(5-6)) in 23 patients affected by ovarian cancer. The dose of Carbo-Pt was adjusted to residual renal function of patients, evaluated as BCMGFR. No case of acute renal failure was observed with this treatment regimen. Urinary excretion of proteins (albumin, beta2-microglobulin, and retinol-binding protein) and tubular enzymes, measured as markers of tubular damage, increased significantly and transiently only in the first days after chemotherapy, whereas no evidence of chronic nephrotoxic effect was documented. Dose individualization, using the value of BCMGFR, may minimize nephrotoxicity due to Carbo-Pt therapy.

Estimate of body water compartments and of body composition in maintenance hemodialysis patients: comparison of single and multifrequency bioimpedance analysis.

OBJECTIVE: The goal of this study was to compare the adequacy of single and multifrequency bioimpedance analysis (BIA) to evaluate body water compartments, body composition, and nutritional status in maintenance hemodialysis patients. DESIGN: Cross-sectional study. SETTING: University-based hemodialysis unit. PATIENTS: Nineteen patients (12 male, 7 female), ages 28 to 82 years (mean, 58.9), treated with maintenance hemodialysis (MHD) for 0.5 to 15 years (mean, 7.3). INTERVENTION: This was a noninterventional study. Patients gave their informed consent to the diagnostic procedures performed. MAIN OUTCOME MEASURES: Total body water (TBW), extracellular water (ECW), fat-free mass (FFM), and body cell mass (BCM) volumes were estimated with single-frequency (sf BIA) and multifrequency (mf BIA) plethysmographs before and after a midweek dialytic session. Predialysis TBW also was estimated from anthropometric data (e TBW). Serum albumin, prealbumin and myoglobin, and creatinine index were determined as indicators of nutritional status and muscle mass. RESULTS: Sf BIA and mf BIA gave very similar results for TBW volumes. A high linear correlation was also found between e TBW values and both sf TBW and mf TBW; however, a statistically significant difference was found between e TBW and sf and mf TBW. Sf BIA and mf BIA gave quite different results for ECW, particularly when measured predialysis. The results obtained for FFM indicate a poor agreement between sf and mf BIA. The agreement was better when FFM was measured postdialysis. The values of BCM, either measured predialysis or postdialysis, indicate a significant difference between sf and mf BIA. FFM and BCM estimated with mf BIA had a closer correlation with creatinine index than sf BIA. mf BCM had also a higher correlation with serum myoglobin, which is produced by muscle cells. CONCLUSIONS: TBW can be estimated with enough confidence from either sf or mf BIA at any time. On the contrary, the results of ECW are significantly different with sf and mf BIA when measured predialysis. Thus, it seems more convenient to perform BIA after dialysis, in particular when assessing the "ideal" body weight. The measurements of FFM and BCM, obtained with either sf or mf BIA, are correlated with different indicators of nutritional status. In particular, mf BCM seems more appropriate than sf BCM for estimating muscle mass.

Prediction of glomerular filtration rate from body cell mass and plasma creatinine.

The gold standards for the measurement of glomerular filtration rate (GFR) are inulin clearance and radioisotopic methods. However, creatinine clearance is the most used test to evaluate GFR in clinical practice. Its adequacy is questionable, since its repeatability is quite poor, mainly due to errors in the collection of urine. The aim of this study was to evaluate a new method to predict GFR from the body cell mass (BCM) and plasma creatinine (Pcr), avoiding urine collection. The values of BCM were obtained in 275 adult renal patients with different renal function, ranging from normality to advanced renal failure. The relationship of GFR (clearance of (99m)Tc-DTPA) with BCM and Pcr was calculated in the first 85 patients. A highly significant linear correlation was found between GFR and the ratio BCM/Pcr. Thereafter, GFR was predicted from BCM and Pcr (BCM GFR) with formulas derived from the relationships found between GFR and the ratio BCM/Pcr. For comparison, GFR was predicted also according to other prediction formulas: Cockcroft and Gault (CG GFR), and the simplified MDRD formula (MDRD GFR). BCM GFR gave a more precise estimate of GFR than CG GFR and MDRD GFR. In fact, BCM GFR had the best correlation and agreement with true GFR ((99m)Tc-DTPA). Furthermore, CG GFR and MDRD GFR markedly overestimated true GFR. Finally, the error of prediction of BCM GFR was definitely lower than that of the two other estimates of GFR. GFR can be predicted from BCM and plasma creatinine. This method, which is very simple and accurate, seems suitable to establish the adequate dosage of drugs cleared by the kidneys.

Serum levels of beta-trace protein and glomerular filtration rate--preliminary results.

The aim of this study was to evaluate the relationship between serum levels of beta-trace protein (BTP), a low molecular weight (MW) protein, and glomerular filtration rate (GFR). GFR and serum levels of BTP, and for comparison creatinine (Creat), cystatin C (Cys) and beta 2-microglobulin (beta 2M), were measured in 60 patients, with renal function ranging from normality to advanced renal failure. Serum levels of BTP progressively increased with the reduction of GFR. A good correlation was found between GFR and serum levels of BTP (r=0.918), Creat (r=0.932), Cys (r=0.937), and beta 2M (r=0.924). Furthermore, no statistically significant difference was found between BTP and Creat, Cys, beta 2M, as indicators of a moderate GFR impairment. These preliminary data indicate that BTP might be suitable as an indicator of GFR.

Renal impairment in patients with ovarian cancer.

OBJECTIVE: To investigate the prevalence of renal impairment in patients with ovarian cancer at the time of the diagnosis. STUDY DESIGN: Creatinine clearance was estimated according to Cockcroft and Gault (C&G Ccr), glomerular filtration rate (GFR) was determined as renal clearance of 99mTc-DTPA, and renal ultrasound was performed in 60 consecutive patients with newly diagnosed ovarian cancer. RESULTS: A 28% of the total population studied had a GFR <60 ml/min/1.73 m(2). A moderate/severe dilation of the upper urinary tract was found in 12% of patients. The length of kidneys ranged between 9.0 and 13.5 cm, and a statistically significant correlation was found between kidney length and values of GFR. CONCLUSION: A reduction in renal function and a moderate to severe dilation of upper urinary tract frequently occur in patients with ovarian cancer at the time of the diagnosis.