Renal Secondary Hyperparathyroidism Research Articles

Fracture mandibulaire chez un Lhassa Apso avec hyperparathyroïdie secondaire rénale

A Lhassa Apso is presented in emergency after having been injured by another dog. It was suffering from a mandibular fracture. The clinical exam revealed generalized and excessive mobility of the whole dentition. Radiographs showed generalized jaw bone demineralisation. A blood sample was analysed and revealed chronic renal disease. We came to the conclusion that this dog was suffering from secondary renal hyperparathyroidism. The hypocalcified bone was so thin that a slight trauma induced the mandibular fracture.

Survival after Parathyroidectomy in Patients with End‐stage Renal Disease and Severe Hyperparathyroidism

Patients with end-stage renal disease (ESRD) and secondary hyperparathyroidism (SHPT) are at high risk of mortality. Whether an increased risk of death persists after a parathyroidectomy (PTX) is not clearly established. The survival of 40 patients with ESRD and SHPT who underwent PTX was compared with that of 664 ESRD patients. From first dialysis, a lower mortality rate was found in the group of patients who underwent PTX than in the nonoperated ESRD group (hazard ratio: 0.23; 95% CI: 0.14-0.37). The patients who underwent PTX were younger, had a longer time on dialysis, and had a higher prevalence of kidney transplantation. The mean number of comorbidities was lower (Charlson score 4.2 +/- 2.1 versus 6.4 +/- 2.9, p < 0.001). Then, we randomly selected two matched controls for each PTX case (80 controls, 40 PTX) who had at least an equivalent mean duration of dialysis between the first dialysis and PTX of the PTX group. In a univariate model, there was a trend for PTX being associated with prolonged survival. The mortality was higher both among those at an advanced age and those with a high Charlson score. Adjustments for these covariates made the effect of PTX no more significant. The risk of death of patients with severe SHPT leading to PTX differed from that of nonoperated subjects. The apparent differences in survival may be related to the number and severity of associated comorbidities. ESRD patients who undergo PTX may represent a subset of healthier subjects.

Complicações cardiovasculares em criança com insuficiência renal crônica

This is the report of an 11-year-old boy with chronic renal disease and secondary hyperparathyroidism. The child had been on dialysis, calcitriol, calcium carbonate, and presented dyslipidemia and calcified thrombi in various vessels and organs in the course of his condition. Pathological examination showed ischemic cerebral necrosis, calcification in coronary arteries, and myocardial infarction.

Renal transplant and secondary hyperparathyroidism

To investigate the impact of mineral metabolism, renal function, months on dialysis and months since transplant for predicting intact parathyroid hormone (iPTH) levels in a cohort of patients who had undergone their first renal graft with estimated glomerular filtration rates (eGFRs) of 30-60 and >60 ml/min/1.73 m2. One hundred and twenty-eight patients (mean age 56.0 +/- 14.6 years) with an eGFR of >30 ml/min/1.73 m2 were included. The median time since transplant was 88.6 months (range 2.8-403.2 months). Blood samples were collected for measurement of iPTH, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, calcium, albumin, phosphate and creatinine. The eGFR was calculated using the formula for the modification of diet in renal disease. One hundred and three patients (80%) had an elevated level of iPTH, 29 (23%) had hypercalcaemia and 42 (35%) had a 25-hydroxyvitamin D3 level of <40 nmol/L. In stepwise backward regression, eGFR and 25-hydroxyvitamin D3 were associated with iPTH, as follows: iPTH = 24.91 -(0.06 x 25-hydroxyvitamin D3) - (0.16 x eGFR) (R2 = 0.14). No associations with these two variables were, however, detected in patients with an eGFR of >60 ml/min/1.73 m2. Forty patients (31%) were transplanted pre-emptively, and the iPTH concentrations were significantly lower in these patients. Decreasing eGFR was the single most important variable predicting iPTH level in a cohort of renal transplant patients with an eGFR of 30-60 ml/min/1.73 m2, but not in patients with an eGFR of >60 ml/min/1.73 m2. Patients transplanted pre-emptively had a statistically significantly lower iPTH level compared with patients who had received dialysis.

Current treatment options in secondary renal hyperparathyroidism

Current treatment options in secondary renal hyperparathyroidism

Bone Mineral Density in Two Boxer Dogs Affected by Moderate to End-stage Chronic Renal Failure

, 2002).In moderate CRF, increased phosphaturia promoted by surviving nephrons maintainsthe plasma phosphate concentration toward normal. As soon as GFR drops below about20% of the normal rate, renal adaptive effects are maximized and hyperphosphatemia en-sues, inducing a related degree of renal secondary hyperparathyroidism and consequentosteodystrophy (Lemann

Concentração sérica de paratormônio intacto em cães com insuficiência renal crônica

Estudou-se a ocorrência de hiperparatireoidismo secundário renal e determinaram-se as concentrações séricas de paratormônio intacto (PTHi-c), cálcio total e fósforo em 30 cães com insuficiência renal crônica (IRC) e em 40 cães sadios. Para a determinação do PTHi-c, foi utilizado o método imunofluorométrico, com o emprego de anticorpos anti-aminoterminal (extraídos de gema de ovo da galinha) e de anticorpos monoclonais anti-carboxiterminal (H5P10), marcados com Europium. As concentrações séricas de PTHi-c (717,23±469,13pg/ml no grupo IRC e 36,76±34,40pg/ml no grupo-controle; P=0,0001), cálcio total (11,46±2,03mg/dl no grupo IRC e 10,11±0,91mg/dl no grupo-controle; P=0,003) e fósforo (12,01±8,06mg/dl no grupo IRC e 4,33±0,74mg/dl no grupo-controle; P=0,0001) foram mais altas nos cães com IRC. Observou-se estreita correlação entre PTHi-c e fósforo (r=0,56; P=0,0006), o que não ocorreu entre PTHi-c e cálcio. Hipercalcemia em cães com alta concentração de PTHi-c demonstrou a possível ocorrência de hiperparatireoidismo terciário em 11 animais. A hiperfosfatemia pode indicar, de forma indireta, a ocorrência de hiperparatireoidismo secundário nos cães com IRC.

Carcinoma paratiroideo sobre trasplante autólogo tras paratiroidectomía total en el hiperparatiroidismo renal

Parathyroid carcinoma usually develops in association with primary hyperparathyroidism. Only 18 cases have been reported in patients with secondary or tertiary renal hyperparathyroidism. We present a case of parathyroid carcinoma arising on transplanted parathyroid tissue after total parathyroidectomy for renal hyperparathyroidism.

Fatal Childhood Calciphylaxis in a 10‐Year‐Old and Literature Review

Calciphylaxis is a rare but highly morbid disorder of vascular calcification and skin necrosis, affecting 1% to 4% of adults with end-stage renal disease. Only three affected children have previously been described. We report an unusual instance of fatal calciphylaxis involving a 10-year-old boy, in the setting of sarcoidosis-induced end-stage renal disease. A review of pediatric calciphylaxis cases suggests: (a) increased risk in boys with end-stage renal disease and secondary hyperparathyroidism; (b) frequent distal extremity and visceral organ involvement, (c) worse prognosis with acral necrosis, and (d) possible increased resistance to medical treatment compared to adult patients. Hyperesthetic pain is a common sentinel symptom, and soft tissue x-rays or xeroradiography or both may aid in the diagnosis of pediatric calciphylaxis. Parathyroidectomy in combination with supportive medical management may be the best treatment option in stopping the progression of disease in the pediatric population.

Calciphylaxis – a topical overview

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.

Complete Resolution of Severe Diarrhoea after Conversion from Mycophenolate Mofetil to Enteric-coated Mycophenolate Sodium (myfortic??) in a Patient at High Immunological Risk

The patient, a 49-year-old man, was diagnosed with end-stage renal failure as a result of chronic glomerulonephritis in 1986. After 5.5 years of haemodialysis, the patient received a first renal allograft in January1992. Sixmonths later, however, the patient experienced a dextrocerebral haemorrhage with sinistral hemiparesis, and rapid chronic transplant vasculopathy was diagnosed. Haemodialysiswas restarted and continued until a second renal transplant was undertaken in February 2002. Concomitant illnesses at the time of transplantation included renal anaemia, hypertension and secondary hyperparathyroidism, which necessitated a parathyroidectomy before transplantation. The second renal transplant proceeded without complications and postoperative dialysis was not necessary. Details of the transplantation are shown in table I. The patient’s hospital stay was uneventful, with no infections or episodes of acute rejection, and he was discharged with stable creatinine values of 150mmol/l, and details of the serum creatinine levels are shown in figure 1. The initial immunosuppressive regimen comprised cyclosporine microemulsion (CsA-ME; 150mg twice a day, trough level 130–150 ng/ ml), mycophenolate mofetil (MMF; 1000mg twice a day) and corticosteroids (day 0, 500mg intravenously; day 1, 250mg intravenously; day 2, 125mg intravenously, then 100mg/day by mouth) with antithymocyte globulin for 7 days (ATGFresenius; 5mg/kg per day). After 3 months, the CsA-MEmaintenance dose was reduced to 100mg twice a day (trough level 80–100 ng/ml). The steroid dose was tapered over the first 3 months post-transplant to a maintenance dose of 5mg/day. The patient experienced occasional bouts of diarrhoea that did not initially require any treatment. Cytomegalovirus seroconversion (pp65 positive) occurred several times and was successfully treated, initially with ganciclovir and subsequently with valganciclovir. In October 2003, cytomegalovirus-associated colitis was diagnosed by coloscopy and histological analysis. This was treated with intravenous ganciclovir and also required a reduction of the MMF dose from 1000mg twice a day to 500mg twice a day. The CsA-ME dose was increased (trough level 150 ng/ml) to ensure adequate immunosuppressant coverage. Serum creatinine was in the range 141–159mmol/l. Three months later, the patient complained of a substantial increase in the number of bouts of diarrhoea. Episodes started approximately 2 h after each dose of MMF, and were becoming more frequent over time, reaching 10–15 episodes a day, with approximately 3 kg weight loss in one week. CASE REPORT Drugs 2006; 66 Suppl. 2: 25–27 0012-6667/06/0002-0025/$44.95/0

Current treatment options in secondary renal hyperparathyroidism

Current treatment options in secondary renal hyperparathyroidism

Kalziphylaxie bei terminaler Niereninsuffizienz als seltene Ursache für Ulcera crurum

Calciphylaxis is a potentially life-threatening disease that occurs up to 4% of patients with chronic terminal renal failure and secondary hyperparathyroidism. Clinical symptoms are painful skin erythema and ischemic necrosis as a result of calcification of the small and medium-sized arteries of the subcutaneous tissues. The mortality of the disease is as high as 87% mainly due to sepsis from superinfection. We report on a 59-year-old patient with chronic renal failure and normal calcium-phosphate-product with leg ulcers as a rare manifestation of a calciphylaxis. In spite of an early parathyroidectomy and a temporary complete wound-healing the death because of calciphylaxis could not be prevented.

Tratamiento quirúrgico del hiperparatiroidismo secundario recidivado

Secondary renal hyperparathyroidism (SHPT) affects nearly all patients on regular hemodialysis. Between 5% and 10% will need surgery to control the disease. Despite a meticulous technique, the rate of recurrent/persistent hyperparathyroidism after surgery remains between 2% and 12%. We reviewed the reoperations of 7 patients with recurrent or persistent SHPT from a series of 56 patients, 3 of which were referred from other units for treatment of recurrence. Subtotal parathyroidectomy (ST-PTX) was performed in 51 patients and total parathyroidectomy with autograft (TPTX-AT) was performed in the remaining 5 patients. Seven patients underwent reoperation for recurrent SHPT, 1 of them twice (8 reinterventions in 56 patients). In 2 patients only 3 parathyroid glands were removed at the first intervention and recurrence was due to the presence of a fourth gland. In 4 patients, ST-PTX was performed and recurrence was due to a remnant hyperplasic area in 1 and to a fifth gland in 3. Recurrence in the patient with a TPTX-AT was to due to cervical parathyromatosis. All the patients with recurrence had a positive preoperative Tc-MIBI scintigraphy and the computed tomography/magnetic resonance examination was highly useful for anatomical localization of the lesion and for planning the surgical approach.

Progression of secondary hyperparathyroidism involves deregulation of genes related to DNA and RNA stability

Renal secondary hyperparathyroidism in its late stages becomes autonomous, so excessive parathyroid hormone (PTH) secretion no longer responds to physiologic stimuli or to aggressive medical treatment. To gain molecular understanding of progression of renal secondary hyperparathyroidism, normal and hyperplastic parathyroid tissue with diffuse and nodular growth were analyzed. The results were also compared to parathyroid adenomas. The analysis was performed by high-density oligonucleotide microarray and bidirectional subtraction library. Analysis of the DNA arrays found 16 overexpressed and 132 repressed genes in the nodules while the subtraction library produced 34 overexpressed and 40 repressed genes. The differentially expressed genes between diffuse and nodular samples included some related to DNA stability and repair (TALDO1, PRDX2, DDB1, XRCC1, and POLB), RNA stability and degradation (OASL and AUF1), protein synthesis and processing (PFDN5, HSPD1, and NACA), cell growth (CDC25C and GRPR), and tumorigenesis and cell cycle (VIL2 and TPD52). According to the function described for the deregulated genes, when secondary hyperparathyroidism becomes autonomous and refractory to treatment, RNA degradation may be increased while DNA integrity may be compromised. These two mechanisms, combined with deregulation of genes related to growth and differentiation show the complex pathway of parathyroid glands' evolution in renal hyperparathyroidism and may explain the large amount of molecular cytogenetic aberrations found in refractory hyperparathyroidism. Considering that some of the genes with altered expression in nodular hyperplasia lead to irreversible consequences in the genomic integrity of the cells, an adequate and early management of the secondary hyperparathyroidism of chronic kidney disease becomes mandatory.

Spontaneous and simultaneous rupture of both quadriceps tendons in a patient with chronic renal failure

Spontaneous bilateral rupture of the quadriceps tendons without a significant history of trauma is an uncommon disease. It is generally associated with chronic metabolic disorders such as chronic renal failure and secondary hyperparathyroidism. Here, we report a case of spontaneous bilateral tendon rupture in a patient on chronic hemodialysis for the past 5 years. We performed a preoperative MRI to confirm the diagnosis; then we repaired the ruptured quadriceps tendons and reviewed the patient both clinically and by performing MRI postoperatively 4 yrs later. The patient attained the full function of the quadriceps tendon.

Osteoporosis in Adult Survivors of Adolescent Cardiac Transplantation May Be Related to Hyperparathyroidism, Mild Renal Insufficiency, and Increased Bone Turnover

Osteoporosis is common in adults who undergo cardiac transplantation. We hypothesized that adolescent cardiac transplant recipients also develop osteoporosis, which would persist into adulthood. We evaluated 9 adult survivors of adolescent cardiac transplantation, aged 21-32, in a cross-sectional, case-control study comparing bone mineral density, indices of mineral metabolism, and bone turnover markers. Osteoporosis (Z score < or = -2.0) was present in 56% of transplant recipients at the lumbar spine, 33% at the femoral neck, and 100% at the one-third radius. Subjects had mean bone mineral density Z scores of -2.3 +/- 0.9 at the spine, -1.6 +/- 0.7 at the femoral neck, and -3.2 +/- 0.7 at the one-third radius, significantly lower than controls at all sites (p < 0.001). Serum creatinine and vitamin D metabolites were normal and did not differ between subjects and controls. Serum calcium was lower, blood urea nitrogen was elevated, and creatinine clearance tended to be lower in transplant recipients. Parathyroid hormone (PTH) levels were 3-fold higher in subjects than controls, and 75% of subjects had elevated PTH levels. Markers of bone turnover were significantly higher in subjects than controls. Adult survivors of adolescent cardiac transplantation have mild renal insufficiency, secondary hyperparathyroidism, and biochemical evidence of increased bone turnover. Osteoporosis is common in these patients, particularly at the one-third radius, a site sensitive to the catabolic effects of sustained excessive PTH secretion. We conclude that adult survivors of adolescent cardiac transplantation should be evaluated for hyperparathyroidism and osteoporosis.

Four gland parathyroidectomy without reimplantation in patients with chronic renal failure

Background: The optimal surgical management of patients in end stage chronic renal failure with secondary hyperparathyroidism is controversial. One approach advocated is four gland parathyroidectomy without reimplantation. The aim of...

Daily or Intermittent Calcitriol Administration during Growth Hormone Therapy in Rats with Renal Failure and Advanced Secondary Hyperparathyroidism

Growth hormone (GH) improves growth in children with chronic renal failure. The response to GH may be affected by the degree of secondary hyperparathyroidism and concurrent treatment with vitamin D. Forty-six rats underwent 5/6 nephrectomy (Nx) and were given a high-phosphorus diet (Nx-Phos) to induce advanced secondary hyperparathyroidism and divided into the following groups: (1) Nx-Phos (n = 10) received saline, (2) GH at 10 IU/kg per d (Nx-Phos+GH; n = 9), (3) GH and daily calcitriol (D) at 50 ng/kg per d (Nx-Phos+GH+daily D; n = 8), (4) GH and intermittent D (three times weekly) at 350 ng/kg per wk (Nx-Phos+GH+int D; n = 9), and (5) intact-control (n = 10). Serum parathyroid hormone (PTH) levels were elevated in Nx-Phos, but IGF-I levels did not change with growth hormone. Body length, tibial length, and growth plate width did not increase with either GH or calcitriol. Proliferating cell nuclear antigen staining, PTH/PTHrP receptor, bone morphogenetic protein-7, and fibroblast growth factor receptor-3 expression increased with GH alone or with intermittent calcitriol but were slightly diminished during daily calcitriol administration. GH enhanced IGF-I, IGF binding receptor-3, and GH receptor but declined with daily and intermittent calcitriol. Overall, there was no improvement in body length, tibial length, and growth plate width at the end of GH therapy, but selected markers of chondrocyte proliferation and chondrocyte differentiation increased, although these changes were attenuated by calcitriol. The combination of GH and calcitriol that is frequently used in children with renal failure and secondary hyperparathyroidism require further studies to evaluate the optimal dose and frequency of administration to increase linear growth and prevent bone disease.

A randomised study on a new cost-effective algorithm of quick intraoperative intact parathyroid hormone assay in secondary hyperparathyroidism

The use of intraoperative intact parathyroid hormone (iPTH) assay in secondary renal hyperparathyroidism (SHP) has been limited by the relatively low cost effectiveness of the assay in improving the success rate for primary bilateral neck exploration. The study aimed at determining, in a prospective, randomised trial, the cost effectiveness and impact of the routine employment of a "six-sample" versus "two-sample" algorithm of the intraoperative iPTH assay during surgery for SHP on intraoperative decision making and surgical success rate. One hundred and two consecutive patients with severe SHP and qualified for subtotal parathyroidectomy were randomly allocated to two equal-sized groups: group A, in which the intraoperative iPTH serum level was determined in six consecutive samples: preoperative, pre-excision, 5, 10, 20 and 60 min, and group B, in which the intraoperative iPTH serum level was determined twice only: preoperatively and 10 min. The STAT intraoperative intact-PTH immunoassay was employed. In group B, in patients with serum iPTH decrease lower than 60% of the baseline at 10 min, an additional measurement was performed at 20-min post-excision. If a decrease of 80% or more of the baseline was not obtained, the exploration was extended in search of remaining hyperfunctioning parathyroid tissue. The surgical success rate was 96.1% and 98.0% (in group A and B, respectively). The impact of the intraoperative iPTH assay on surgical decision making was demonstrated in 13.7% and 15.7% (in group A and B, respectively). The assay was helpful in identifying patients with supranumerary hyperfunctioning parathyroid tissue (5.9% vs 7.8% in group A and B, respectively), patients with fewer than four parathyroid glands (3.9% vs 5.9% in group A and B, respectively) and patients with remaining hyperfunctioning parathyroid tissue suspected to be located within the mediastinum in cases of negative bilateral neck exploration who benefit from transcervical thymectomy. The diagnostic accuracy of the intraoperative iPTH assay was 100% in both groups. The accuracy of two-sample algorithm increased from 96% to 100% if an additional serum iPTH determination was performed in borderline cases with an iPTH drop lower than 60% of the baseline at 10 min. The cost-effectiveness analysis showed significant savings in group B, equal to Euro 87.6 per patient, with the unchanged diagnostic accuracy of the two-sample algorithm. The intraoperative iPTH assay in patients operated on for secondary hyperparathyroidism offers support in surgical decision making in the majority of patients, allowing for correct identification of patients with supranumerary ectopic hyperfunctioning parathyroid glands, and in patients with fewer than four parathyroid glands. It also correctly identifies patients who do not benefit from blind thymectomy. The two-sample algorithm, extended to include three determinations in selected cases, has the same 100% diagnostic accuracy as the six-sample algorithm, the former being a much more cost-effective procedure.