Impaired bone microarchitecture and strength in patients with tumor-induced osteomalacia.

Some studies based on bone biopsy have demonstrated that in patients with tumor-induced osteomalacia (TIO) the mineralization process of the bone matrix is profoundly disturbed. However, the interrelationship between clinical and biochemical features and bone microarchitecture in this disease needs further analysis. With this purpose in mind, we set out three objectives: (i) to determine bone microarchitecture and estimated bone strength in a group of patients with tumor-induced osteomalacia using high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA), (ii) to investigate correlations between duration of disease, biochemical features, bone density, HR-pQCT and FEA parameters, and (iii) to compare HR-pQCT and FEA parameters with a healthy control group. Ten patients with TIO were included. All patients had non-resolved disease. At the distal radius, all bone microarchitecture parameters were significantly affected in patients with TIO in comparison with healthy controls. At the distal tibia, all parameters were significantly impaired, except for trabecular thickness. All the parameters were more affected in the distal tibia than in the distal radius. Women with TIO (n = 7) had significantly lower bone strength parameters than healthy controls. In men (n = 3), bone strength parameters were significantly lower than in the control group at the distal tibia. Alkaline phosphatase levels exhibited a negative correlation with microarchitecture parameters, failure load, and stiffness. Higher levels of parathyroid hormone correlated with poorer microarchitecture parameters. We believe that in TIO, hormonal disturbances and the lack of mechanical stimulus specially converge to generate an extremely harmful combination for bone health. © 2021 American Society for Bone and Mineral Research (ASBMR).

Biochemical diagnosis in 3040 kidney stone formers in Argentina.

Nephrolithiasis is a frequent condition in urology that has an important recurrence and high impact in health economy. Knowing the biochemical abnormalities implicated in its pathogenesis is mandatory to establish therapeutic aims. Our objectives are to present the results in 3040 kidney stone formers in Argentina. All patients were selected after completing an ambulatory metabolic protocol with diagnostic purposes. There were 1717 men, (56.48%), with a mean age of 45±12 years, and 1323 women, (43.52%), mean age 44±12 years. 2781 patients had biochemical abnormalities, (91.49%), and were arbitrarily divided in two groups: those who had only one (single) biochemical abnormality (n=2156) and those who had associated abnormalities (n=625). No biochemical abnormalities were found in 259 patients (8.51%). The abnormalities present, single and associated, in order of frequency, were idiopathic hypercalciuria, (56.88%), hyperuricosuria (21.08%), unduly acidic urine (10.95%), hypocitraturia (10.55%), hypomagnesuria (7.9%), primary hyperparathyroidism (3.01%), hyperoxaluria (2.6%), and cystinuria (0.32%). We performed in 484 patient's stone composition and found calcium oxalate stones related to idiopathic hypercalciuria predominantly while uric acid stones to unduly acidic urine. In conclusion, the biochemical abnormalities described are similar to those found in a previous series of our own and to those reported in the literature. Its diagnosis is important to therapeutic purposes to avoid eventual recurrence.

Weekly high-dose ergocalciferol to correct vitamin D deficiency/insufficiency in hemodialysis patients: a pilot trial.

Controversy exists on which vitamin D (D2 or D3) and which dosage scheme is the best to obtain and maintain adequate 25 OH D levels in dialysis patients safely. We tried to determine whether high-dose vitamin D2 supplementation could obtain optimal vitamin D status without inducing hypercalcemia. We studied 82 patients on dialysis not taking active vitamin D therapy and supplemented them with oral vitamin D2 72,000 IU/week for 12 weeks followed by 24,000 IU/week as maintenance therapy during 36 weeks. By week 12, serum 25(OH)D increased from 15.2 ± 5.4 to 42.5 ± 13.2 ng/mL (P < 0.01) at week 12 and remained optimal (34.7 ± 12.0); 84.8% of the patients reached values ≥30 ng/mL. iPTH and alkaline phosphatase did not change at 48 weeks compared with baseline, but bone alkaline phosphatase decreased significantly (54.3 ± 46.0 to 44.3 ± 25.0; P = 0.02). Uncorrected serum Ca increased significantly at the end of follow-up (9.03 ± 0.42 to 9.14 ± 0.62; P = 0.04); hypercalcemia was presented in two patients in the first control visit (week 12), in one patient in the second control (week 30), and in one patient in the third control (week 48). In 222 serum calcium determinations during follow-up, hypercalcemia was observed in only 1.8% of cases. This vitamin D2 oral regimen with initial high doses was safe and sufficient to obtain and maintain optimal serum 25(OH)D concentrations and prevent vitamin D insufficiency in chronic kidney disease patients on dialysis.

Persistence of hypercalciuria after successful surgical treatment for primary hyperparathyroidism.

UNLABELLED: Primary hyperparathyroidism (PHPT) causes hypercalciuria and stone disease in a subset of patients. Hypercalciuria typically normalizes after surgery, although the risk of stone formation may persist up to 10 years. There are few reports in the literature that show persistent hypercalciuria despite normalization of serum calcium after parathyroid surgery. We retrospectively analyzed 111 patients with PHPT from the osteoporosis, and stone clinics seen between 1999 and 2006. We selected only patients who had a complete metabolic profile that included 24-hour collections before and at least 3 months after parathyroidectomy. We excluded patients who had creatinine clearance <60 ml/min/1.73 m(2). Fifty-four patients were selected for further analysis, 46 with baseline hypercalciuria and 8 with normocalciuria. Changes in filtered load of calcium and fractional excretion of calcium were evaluated before and after parathyroid surgery. Total and ionized calcium and phosphorus normalized in all patients after surgery (24 ± 19 months); fractional excretion of calcium decreased, but did not normalize. Hypercalciuria persisted after surgery in 30.7% (n = 12/39) of the women and 50% (n = 4/8) of men. Of the patients in whom calciuria normalized after parathyroidectomy, 43.3% (n = 13/30) had kidney stones before surgery, whereas kidney stones were present in 87.5% (n = 14/16) in those in whom hypercalciuria persisted postsurgery. In hypercalciuric men and women before surgery in whom hypercalciuria persisted after surgery, fractional excretion of calcium was significantly higher than that in patients with normocalciuria. CONCLUSIONS: Persistently increased fractional excretion of calcium could explain the sustained increased risk of stone disease in patients with PHPT for many years after successful parathyroidectomy.

Metabolic risk factors in children with kidney stone disease.

The evaluation of metabolic risk factor in children with renal stone disease is the basis of medical treatment aimed at preventing recurrent stone events and the growth of preexisting calculi. In this retrospective study, we evaluated the metabolic risk factors and clinical and family histories of 90 children with kidney stone disease who had been referred to our institution and subjected to clinical tests using a standardized protocol. The mean age of our pediatric patients was 10.7 years, and the male:female ratio was 1.14:1.0. Biochemical abnormalities were found in 84.4% of all cases. A single urine metabolic risk factor was present in 52.2% (n = 47) of the patients, and multiple risk factors were present in the remaining 31.1% (n = 28). Idiopathic hypercalciuria (alone or in combination) and hypocitraturia (alone or in combination) were the most frequent risk factors identified in 40 and 37.8% of these patients, respectively. Renal colic or unspecified abdominal pain were the most frequent forms of presentation (76.9%), with 97.5% of stones located in the upper urinary tract. In most patients, stone disease was confirmed by renal ultrasonography (77%). A positive family history in first-degree and second-degree relatives was found in 46.2 and 32.5% of the cases, respectively. We conclude that specific urine metabolic risk factors are found in most children with kidney stones and that hypocitraturia is as frequent as hypercalciuria. Very often there is a positive family history of renal stone disease in first- and second-degree relatives.

Clinical and biochemical profile of patients with "pure" uric acid nephrolithiasis compared with "pure" calcium oxalate stone formers.

The purpose of the present study was to compare the clinical characteristics of "pure" uric acid (UA) stone formers with that of "pure" calcium oxalate (CaOx) stone formers and to determine whether renal handling of UA, urinary pH, and urinary excretion of promoters and inhibitors of stone formation were different between the two groups. Study subjects comprised 59 patients identified by records of stone analysis: 30 of them had "pure" UA stones and 29 had "pure" CaOx nephrolithiasis. Both groups underwent full outpatient evaluation of stone risk analysis that included renal handling of UA and urinary pH. Compared to CaOx stone formers, UA stone formers were older (53.3 +/- 11.8 years vs. 44.5 +/- 10.0 years; P = 0.003); they had higher mean weight (88.6 +/- 12.5 kg vs. 78.0 +/- 11.0 kg; P = 0.001) and body mass index (29.5 +/- 4.2 kg/m(2) vs. 26.3 +/- 3.5 kg/m(2); P = 0.002) with a greater proportion of obese subjects (43.3% vs. 16.1%; P = 0.01). Patients with "pure" UA lithiasis had significantly lower UA clearance, UA fractional excretion, and UA/creatinine ratio, with significantly higher serum UA. The mean urinary pH was significantly lower in UA stone formers compared to CaOx stone formers (5.17 +/- 0.20 vs. 5.93 +/- 0.42; P < 0.0001). Patients with CaOx stones were a decade younger, having higher 24-h urinary calcium excretion (218.5 +/- 56.3 mg/24 h vs. 181.3 +/- 57.1 mg/24 h; P = 0.01) and a higher activity product index for CaOx [AP (CaOx) index]. Overweight/obesity and older age associated with low urine pH were the principal characteristic of "pure" UA stone formers. Impairment in urate excretion associated with increased serum UA was also another characteristic of UA stone formers that resembles patients with primary gout. Patients with pure CaOx stones were younger; they had a low proportion of obese subjects, a higher urinary calcium excretion, and a higher AP index for CaOx.

Prevalence of 25(OH) vitamin D insufficiency and deficiency in chronic kidney disease stage 5 patients on hemodialysis.

Little is known about the magnitude of vitamin D deficiency in patients with stage 5 chronic kidney disease (CKD-5) on hemodialysis (HD). In the present study, we examined the prevalence of vitamin D deficiency in patients with CKD-5 undergoing HD, evaluating the relationship between calcidiol levels with other parameters of mineral metabolism, nutrition/inflammation, functional capacity (FC), and sunlight exposure. Serum 25(OH) vitamin D levels were evaluated in 84 stable patients on chronic HD not receiving vitamin D supplements, with a mean age 58.9+/-16.6 years, during the month of September (end of winter in the southern hemisphere). 25(OH) vitamin D serum levels, intact PTH (iPTH), as well as serum albumin, calcium, phosphorus, and alkaline phosphatase were analyzed in fasting samples. Similarly, protein catabolic rate (PCR) and body mass index (BMI) were determined as nutritional parameters. Functional capacity according to the Karnofsky index, and sunlight exposure were also analyzed. In this study, we considered adequate vitamin D levels those above 30 ng/mL (U.S.A. National Kidney Foundation DOQI Guidelines), vitamin D insufficiency when levels were between 15 and 30 ng/mL, and vitamin D deficiency when levels were below 15 ng/mL. The mean 25(OH) D levels were significantly higher in men than in women (28.6 vs. 18.9 ng/mL; p=0.001). Vitamin D insufficiency was found in 53.5% of the patients (n=45) and vitamin D deficiency in 22.6% (n=19). In the univariate analysis, there were no correlations between 25(OH) D levels with age, iPTH, calcium, or phosphorus. There were positive correlations between serum 25(OH) D levels and degrees of sunlight exposure (R=0.55; p<0.0001), serum creatinine (r=0.38; p<0.001), serum albumin (r=0.22; p=0.04), and a negative correlation with BMI (r=-0.26; p=0.01). In the multiple regression analysis, only sunlight exposure (B=0.361), BMI (B=-0.23), and gender (B=-0.27) were significantly associated with 25(OH) D levels. Patients with FC 1 to FC 2 (n: 70%, 83.3%) had significantly higher 25(OH) D serum levels compared with FC 3 to FC 4 patients (n: 14%, 16.6%): 25.9 vs. 17.1 ng/mL (p=0.03). These results indicate that vitamin D insufficiency/deficiency is highly prevalent (76.1%) at the end of winter, in stage 5 CKD patients on HD, and lower values seem to be related to decreased sunlight exposure, female gender, increased BMI, and worse functional class.

[Hypocalciuric hypercalcemia due to de novo mutation of the calcium sensing receptor]. / Hipercalcemia hipocalciúrica debida a una mutación de novo del gen del receptor sensor del calcio.

The aim of this paper is to refer the unusual case of a 34 years old woman who consulted because of asymptomatic hypercalcemia, detected in a biochemical routine examination. The elevated values of serum calcium without blunted parathyroid hormone secretion suggested a parathyroid pathology. The concomitance of hypocalciuria with hypercalcemia and a calcium clearance/creatinine clearance ratio less than 0.01 reverted the diagnosis of familial hypocalciuric hypercalcemia, the first option. The absence of familial background led to the molecular study of the patient and her family. The latter confirmed the diagnosis of a de novo inactivating mutation of the calcium sensing receptor. Details on the molecular study and a brief review of this subject are included.

Bone mineral density: serum markers of bone turnover and their relationships in peritoneal dialysis.

BACKGROUND: The usefulness of bone mass measurements and bone turnover markers to estimate the risk of fracture and the type of underlying renal osteodystrophy are not well established in patients on peritoneal dialysis (PD). OBJECTIVE: To assess bone mass using total and regional bone densitometry in a group of patients on PD and to determine if serum markers of bone turnover identify patients with low bone mass. METHODS: Bone densitometry was studied by dual-energy x-ray absorptiometry (DEXA), and bone turnover using several serum markers, in 65 patients on PD. Bone mass was classified as normal, osteopenic, or osteoporotic according to World Health Organization criteria based on bone mineral density (BMD) T scores. RESULTS: T scores in the osteopenia range were present at the lumbar spine (LS) in 44.6% (45% of men and 44.4% of women) of patients and at the femoral neck (FN) in 56.9% (55% of men and 58% of women). T scores in the osteoporosis range were present at the LS in 13.8% of patients (10% of men and 15.5% of women) and at the FN in 21.5% (30% of men and 17.7% of women). Patients with BMD T scores in the osteoporosis range at both regions had increased serum intact parathyroid hormone (iPTH) levels compared to patients in the osteopenic/normal range. Bone mineral content in the whole skeleton (TBMC) correlated negatively with iPTH (r = -0.34) and with total time on dialysis (r = -0.26); in multivariate analysis, only iPTH correlated negatively with TBMC (B = -0.26, p = 0.03). No correlations were found between the other bone markers and BMD T scores at the FN or LS. There were no significant differences in absolute BMD or BMD T scores at the LS or FN between patients with and patients without fractures. CONCLUSIONS: BMD T scores in the osteopenia/osteoporosis range were observed at the LS in 58.4% of these patients on PD and at the FN in 78.4%. TBMC correlated negatively with iPTH. There were no correlations between markers of bone turnover and bone mass measurements at the two skeletal regions, although patients with BMD T scores in the osteoporosis range had increased serum iPTH levels. Bone mass measurements were not different between patients with and patients without fractures.

Intra-assay total uncertainty of results in immunoassay techniques.

Uncertainty is a parameter associated with the result of a measurement; this parameter characterizes the dispersion of the values that could reasonably be attributed to the sample. Data processing methods do not take into account the influence of the imprecision and deviation of the experimental points of the calibration system and their impact on the final result of a sample analysis. The aim of this work is: (a) to propose, for each run, a simple method to calculate the uncertainty due to the calibration system (Uc); and (b) to present a method to determine the "intra-assay total uncertainty" (Ut) and evaluate its impact on the final result for an analyte. Ten replicates of standards, controls, and two serum-male and female samples were measured in the same run with a manual kit for determination of testosterone. To calculate Ut, random duplicate responses were selected. For controls and samples, Ut was affected by Uc (2.91% to 6.59%) and by the uncertainty of the measurement of the sample (Us) (1.01 to 8.73%); this allowed us to determine that Ut had values from 3.73% to 9.87%. While Us affects the result of a given sample, Uc affects the result of all the samples with a similar response (cpm). In the method proposed, Ut involves Us and Uc, both factors that introduce variations into the result of a sample by random causes. Intraassay total uncertainty includes the most probable result for the analytical methodology selected.

Hipercalcemia hipocalciurica debida a una mutacion de novo del gen del receptor sensor del calcio / Hypocalciuric hypercalcemia due to de novo mutation of the calcium sensing receptor

El objetivo de este trabajo es presentar el inusual caso clínico de una paciente de 34 años que consultó para establecer diagnóstico de certeza y conducta terapéutica ante una hipercalcemia asintomática, detectada en un examen dioquímico de rutina. La elevación de la calcemia en ausencia de inhibición de la secreción de parathormona y coincidente con una relación clearance de calcio/clearance de creatina inferior de 0.01, hicieron sospechar el diagnóstico de hipercalcemia hipocalciúrica familiar. La falta de antecedentes familiares llevó a realizar un estudio molecular de la paciente y su grupo familiar. Los resultados de los estudios nos permitieron concluir que la paciente es portadora de una mutación de novo (inactivante) del gen del receptor sensor del calcio. Se incluyen los datos de estudio molecular y una breve revisión bibliográfica del tema.

Hipercalcemia hipocalciúrica debida a una mutación de novo del gen del receptor sensor del calcio. / [Hypocalciuric hypercalcemia due to de novo mutation of the calcium sensing receptor]

The aim of this paper is to refer the unusual case of a 34 years old woman who consulted because of asymptomatic hypercalcemia, detected in a biochemical routine examination. The elevated values of serum calcium without blunted parathyroid hormone secretion suggested a parathyroid pathology. The concomitance of hypocalciuria with hypercalcemia and a calcium clearance/creatinine clearance ratio less than 0.01 reverted the diagnosis of familial hypocalciuric hypercalcemia, the first option. The absence of familial background led to the molecular study of the patient and her family. The latter confirmed the diagnosis of a de novo inactivating mutation of the calcium sensing receptor. Details on the molecular study and a brief review of this subject are included.

Hipercalcemia hipocalciurica debida a una mutacion de novo del gen del receptor sensor del calcio / Hypocalciuric hypercalcemia due to de novo mutation of the calcium sensing receptor

El objetivo de este trabajo es presentar el inusual caso clínico de una paciente de 34 años que consultó para establecer diagnóstico de certeza y conducta terapéutica ante una hipercalcemia asintomática, detectada en un examen dioquímico de rutina. La elevación de la calcemia en ausencia de inhibición de la secreción de parathormona y coincidente con una relación clearance de calcio/clearance de creatina inferior de 0.01, hicieron sospechar el diagnóstico de hipercalcemia hipocalciúrica familiar. La falta de antecedentes familiares llevó a realizar un estudio molecular de la paciente y su grupo familiar. Los resultados de los estudios nos permitieron concluir que la paciente es portadora de una mutación de novo (inactivante) del gen del receptor sensor del calcio. Se incluyen los datos de estudio molecular y una breve revisión bibliográfica del tema. (AU)

Renal phosphate leak in patients with idiopathic hypercalciuria and calcium nephrolithiasis.

Although urine phosphate loss has been associated with hypercalciuria, it is debated how frequently renal phosphate leak is present in hypercalciuric patients. We reviewed the records of 100 consecutive adult patients who were diagnosed with idiopathic hypercalciuria and calcium urolithiasis, searching for the presence of renal phosphate leak. The renal phosphate threshold, normalized for the glomerular filtration rate (TmPO4/GFR), of the hypercalciuric patients followed a normal distribution and had a good correlation with serum phosphate ( r=0.77; p<0.0001). There were no correlations between TmPO4/GFR and urinary calcium or between serum phosphorus and urinary calcium. We found only nine patients (9%) with renal phosphate leak. These patients had a mean TmPO4/GFR of 2.19 mg% (0.70 mmol/l) and serum phosphorus of 2.65 mg% (0.85 mmol/l). Nevertheless, urinary calcium was not significantly different between patients with or without low TmPO4/GFR. We conclude that renal phosphate leak is an infrequent finding in patients with idiopathic hypercalciuria and is not associated with a higher urinary calcium loss.

Niveles de vitamina D en mujeres de la ciudad de Buenos Aires / Vitamin D status in women living in Buenos Aires

La pérdida ósea tiene componentes relacionados con la edad y la menopausia. La pérdida ósea asociada con el progreso de la edad se debe a múltiples factores. Con el fin de evaluar el estado nutricional de vitamina D de mujeres de nuestra ciudad (34ºS), se midió la concentración sérica de calcidiol en 357 mujeres ambulatorias con rango de edad 40-90 años. Ciento ochenta fueran evaluadas en meses de verano y 177 en meses de invierno. También evaluamos niveles de parathormona intacta (PTH) en un subgrupo de 231 mujeres, lo que nos permitió documentar la prevalencia de hiperparatiroidismo secundario. Los valores de calcidiol en verano fueron significativamente más altos que en invierno: 25.3 + 8.5 vs 21.3 + 7.4 ng/ml (p<0.001). Hallamos un 4.4 por ciento de déficit de vitamina D, 2.2 por ciento en verano y 6.6 por ciento en invierno. La prevalencia de calcidiol entre 10-20 ng/ml fue de 67 por ciento en invierno y de 25 por ciento en verano. Un 5.2 por ciento de la mujeres presentó hiperparatiroidismo secundario. Si bien la prevalencia de déficit de vitamina D fue baja comparada con otras series, una gran proporción de mujeres presentó valores entre 10 y 20 ng/ml. Estos valores podrían no ser suficientes para la población adulta y añosa, y resultar en aumento de movilización de calcio y posterior pérdida ósea.

Niveles de vitamina D en mujeres de la ciudad de Buenos Aires / Vitamin D status in women living in Buenos Aires

La pérdida ósea tiene componentes relacionados con la edad y la menopausia. La pérdida ósea asociada con el progreso de la edad se debe a múltiples factores. Con el fin de evaluar el estado nutricional de vitamina D de mujeres de nuestra ciudad (34ºS), se midió la concentración sérica de calcidiol en 357 mujeres ambulatorias con rango de edad 40-90 años. Ciento ochenta fueran evaluadas en meses de verano y 177 en meses de invierno. También evaluamos niveles de parathormona intacta (PTH) en un subgru