Calciphylaxis with histologic changes of pseudoxanthoma elasticum.

Background and Aims The normalization of the function of the parathyroid glands after successful kidney transplantation does not occur in all patients. The aim of our study was to determine of parathyroid function, patient factors that would be predictive of achieving a normal serum PTH in the first months after surgery and prevalence of hyperparathyroidism (HPT) in patients after kidney transplantation (KT) at various stages of the post-transplant period. Method The observational cross-retrospective study included 230 kidney graft recipients. Inclusion criteria: the duration of the post-transplant period is more than 12 months and stable kidney transplant function for 6 months. The median of the pre-transplant stage was 18 months (Q1-Q3: 9; 35), post-transplant period - 42 months (Q1-Q3: 21; 73). Serum concentrations of parathyroid hormone (PTH), calcium, phosphorus, total alkaline phosphatase activity, albumin, and creatinine were determined using standard methods. HPT was diagnosed with PTH>130 pg/ml. Retrospective analysis of parameters in three months after surgery it was performed in 197 patients. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula, stratification of chronic kidney disease (CKD) stages was carried out according to the eGFR. Results Patients had different kidney transplant function: eGFR 117-15 ml/min, median 51 (Q1-Q3: 39;65): CKD 1(КT) st. was in 3.5%, CKD 2(КT) st. - in 33.9%, CKD 3(КT) st. - in 49.1% and CKD 4(КT) st. – in 13.5% patients. Serum PTH levels were 27-670 pg/ml, median 120 pg/ml (Q1-Q3: 87; 182). The median PTH of blood in patients was 99 pg/ml (Q1-Q3: 76; 120), 98 pg/ml (Q1-Q3: 79; 123), 120 pg/ml (Q1-Q3: 89; 180) and 267 pg/ml (Q1-Q3: 170; 328), respectively, with CKD 1(КT), CKD 2(КT), CKD 3(T) and CKD 4(КT) st. The frequency of HPT was 38.7%: 19.8% in patients with eGFR≥60 ml/min, 38.1% and 93.5% in patients with CKD 3(КT) and CKD 4(КT) st. (p<0.001) (Fig. 1). HPT was equally frequently diagnosed in the second, third, fourth and fifth years after kidney transplantation and amounted to 30.3% in the first five years. In patients with a post-transplant period of more than 5 years, HPT was 54.7% (p<0.001). In the same group, the proportion of patients with eGFR<60 ml/min was also higher - 55.5% (p=0.002) (Fig. 2). An inverse relationship was established between serum PTH and eGFR and a direct relationship between serum PTH and serum creatinine (p<0.001). A retrospective analysis showed that 3 months after kidney transplantation, the median PTH was 178 pg/ml (Q1-Q3: 120; 250), HPT was recorded in 65.5% of patients. Serum PTH decreased by 6-92%, median 50%. Kidney graft function was worse in patients with a decrease in serum PTH ≤50% (n = 100) versus patients with a decrease in serum PTH >50% (n = 97). Minimal blood creatinine was recorded in the early postoperative period, respectively, on (median) 7 and 5 days (p = 0.015), the median eGFR by the end of the third month was 59 and 63 ml/min, respectively (p=0.044). We found that preoperative PTH>585 pg/ml (p<0.0001 OR 2.93 95% CI 1.78; 5.05), delayed kidney graft function (p=0.005 OR 1.57 95% CI 1.58; 9.87), and eGFR<60 ml/min (p<0.0005 OR 2.01 95% CI 1.36; 3.09) were predictive of HPT in patients in the early stages after kidney transplantation. Conclusion Hyperparathyroidism in patients after kidney transplantation continues to be an ongoing problem. It occurs in a third of patients in the first five postoperative years and in half patients in subsequent years. Preoperative secondary hyperparathyroidism, delayed and suboptimal kidney graft function prevent the restoration of parathyroid glands function after kidney transplantation.

A patient with hypertension and chronic renal failure of an undetermined cause who was undergoing hemodialysis developed bilateral crusted, focally eroded plaques on her breasts. A biopsy specimen of the lesional skin revealed typical histologic changes of pseudoxanthoma elasticum, with epidermal perforation. A biopsy specimen of lesion-free skin revealed characteristics typical of pseudoxanthoma elasticum. Perforating pseudoxanthoma elasticum should be added to the growing list of cutaneous disorders that occur in patients with chronic renal failure who are undergoing hemodialysis.

Effects of hemodialysis on secondary hyperparathyroidism in patients with chronic renal failure

Disclosure: P. Pile: None. J. Arunachalam: None. P. Madhavan: None.Background: Previous studies have suggested an increased risk of malignancy in patients with primary hyperparathyroidism (PHPT), with one notable association being breast cancer, as highlighted in a 2007 Swedish study by Nilsson et al. Breast cancer is frequently linked to hypercalcemia of malignancy, which is often a sign of skeletal metastases. However, there is limited information on hypercalcemia in patients with breast cancer unrelated to skeletal metastases. Here, we present a retrospective, single institution study evaluating the prevalence of primary hyperparathyroidism in breast cancer. Methods: After receiving exemption from the institutional review board, we conducted a review of electronic medical records from our institution to assess the prevalence of hyperparathyroidism in breast cancer patients between July 2018 to December 2024. We used diagnosis codes for breast cancer and hyperparathyroidism to identify relevant patients. The study population consisted of all patients diagnosed with hyperparathyroidism (HPT), excluding those with chronic kidney disease (CKD), as these individuals might have secondary or tertiary hyperparathyroidism. Specifically, patients with CKD stages 3a, 3b, 4, and 5 were excluded from the analysis. Data collection was performed using Slicer Dicer in Epic, and descriptive statistics were applied to determine the proportion of patients with Vitamin D deficiency and bone metastases in patients with HPT and breast cancer, and prevalence of HPT. To compare prevalence rates, a Chi-square test was used. Results: The study identified 72 female breast cancer patients, aged 73 ± 10 years, who were diagnosed with HPT but did not have CKD. The prevalence of HPT in this group was found to be 2.12% (n=72), which is significantly higher than the prevalence of HPT in general population of 0.11% (n=1862), with a p-value < 0.001. Only 5 patients (0.07%) had distant bone metastases. Only 3 (0.04%) patients had Vitamin D deficiency (25-OH-D <20 ng/mL) at the time of elevated parathyroid hormone (PTH) levels, further supporting that elevated PTH was likely due to PHPT rather than secondary causes. Conclusion: This study reveals a significantly higher prevalence of PHPT in the breast cancer population compared to the general population. This study underscores the importance of evaluating PTH in patients with breast cancer and hypercalcemia even without the presence of bone metastases. Limitations of our study include the inclusion of males in the general population cohort, who have a lower prevalence of breast cancer. To address these limitations, we plan to further analyze patient characteristics in a future study to refine our findings and reduce such confounders.Presentation: Monday, July 14, 2025

Prevention of Renal Osteodystrophy in Predialysis Patients

Low triiodothyronine: a pathway to coronary calcification in patients maintained on peritoneal dialysis

Persistent systemic inflammation has been widely recognized in patients with chronic kidney disease (CKD), and is associated with increased risk of morbidity and mortality. Intervention therapies aiming for the blockade of inflammatory cytokines are considered attractive approaches for CKD patients with signs of chronic inflammation. In this context, thalidomide, due to its potent anti-inflammatory and immunomodulatory properties, may represent an alternative strategy of treatment. In the present study, we developed an experimental model of CKD with uraemia in mice, induced by a diet rich in adenine, which causes progressive renal dysfunction, resembling the human uraemic features. Inflammatory parameters were analysed in this model of CKD and the potential beneficial effects of thalidomide as an anti-inflammatory drug was also investigated. C57/BL-6 mice were fed with an adenine-containing diet during a period of 6 weeks. Thirty mice were divided into three groups: Control group (animals receiving normal diet), ADE group (mice receiving adenine-containing diet) and ADE + TLD group (CKD mice receiving thalidomide, 30 mg/kg/day, by gavage). Besides biochemical and histopathological changes, local and systemic inflammatory parameters were also analysed, including expression of cytokines interleukin (IL)-1β, tumour necrosis factor-α, IL-6, IL-4 and IL-10 in kidney samples by real-time RT-PCR and quantification of serum levels of cytokines. Finally, the electrophoretic mobility shift assay (EMSA) for NF-κB was also examined. Adenine-fed mice developed advanced CKD characterized by a marked increase in serum urea, creatinine, phosphorus and intact parathyroid hormone (iPTH) levels. In addition, histological changes of tubulointerstitial injury, characterized by deposition of crystals in the kidney, accompanied by tubular dilatation, degeneration of proximal tubular epithelium with loss of the brush border, inflammatory cellular infiltration, foreign-body granuloma formation and interstitial fibrosis were also evident. By immunohistochemistry, Mac-2- and α-SMA-positive cells were identified in the tubulointerstitial compartment. Treatment with thalidomide significantly reduced serum urea, creatinine, phosphorus and iPTH levels and protected against tubulointerstitial injury. Local and systemic inflammation in the mice model of adenine-induced CKD was confirmed by the findings of significantly high expression of cytokine mRNA levels and NF-κB activation in the kidney tissue as well as marked increased serum levels of inflammatory cytokines. Thalidomide treatment significantly reduced gene expression of these cytokines and the activation of the NF-κB in the renal tissue and the circulating levels of cytokines. Dietary adenine caused advanced CKD with uraemia in mice providing a useful experimental model to study molecular and morphological changes associated with this disease. The negative impact of inflammation in this CKD model was overcome by the marked anti-inflammatory effects of thalidomide, promoting renal protection.

Outcomes associated with hypogonadism in women with chronic kidney disease

Obesity is associated with secondary hyperparathyroidism in the general population. The objective of this study is to explore whether the same association is present in patients with chronic kidney disease. Linear regression models were used to examine the association between intact parathyroid hormone level and body mass index in 496 male US veterans (age 69.4 +/- 10.2 yr, 22.8% black) who had chronic kidney disease stages 2 to 5 and were not yet on dialysis (estimated GFR 31.8 +/- 11.2 ml/min per 1.73 m2). Higher intact parathyroid hormone was associated with higher body mass index after adjustment for age, race, diabetes, and serum calcium and phosphorus levels. This association was independent of age, race, diabetes status, and serum calcium and phosphorus but was limited to patient groups with lower albumin (P = 0.005 for the interaction term) or higher white blood cell count (P = 0.026 for the interaction term). Higher body mass index is associated with secondary hyperparathyroidism in patients who have chronic kidney disease and are not yet on dialysis, especially in patients with evidence of malnutrition and inflammation. Confirmation of these findings in other patient groups with chronic kidney disease and better characterization of the underlying mechanisms of action will be necessary before advocating weight loss as a means to treat secondary hyperparathyroidism in chronic kidney disease.

Evaluación prospectiva de paratiroidectomías en el tratamiento del hiperparatiroidismo secundario

Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic renal failure (CRF) . Medical treatment may be the first choice for most SHPT patients, but parathyroidectomy (PTX) is needed when medical treatment doesn’t work in patients with refractory SHPT. However, there is no strong evidence to support which surgical procedure is the most effective one for patients with SHPT. An interdisciplinary discussion between nephrologists and surgeons is needed when choosing a preferred surgical method for refractory SHPT patients. The factors must be discussed including: the patient’s age, the underlying kidney disease, clinical symptoms, the level of intact parathyroid hormones (iPTH) and blood calcium, the patient’s ability to obtain and comply with medication treatment and the estimated duration of dialysis before kidney transplantation. Refractory SHPT patients will benefit from the surgical operation treatment and reoperation of recurrent SHPT is still an ideal treatment method. Key words: Chronic renal failure; Secondary hyperparathyroidism; Parathyroidectomy; Intraoperative parathyroid hormone; Autotransplantation

Severe Renal Osteodystrophy in a Pediatric Patient With End-Stage Renal Disease: Sagliker Syndrome?

Primary ectopic mineralization disorders: from (vascular) calcification to syndrome Ectopic mineralization is a pathologic process resulting in inappropriate biomineralization of soft tissues such as the skin and blood vessels. It can be found in frequent western disorders such as chronic kidney disease and diabetes mellitus, though it is also part of a spectrum of primary genetic mineralization disorders such as pseudoxanthoma elasticum (PXE). These heritable disorders are associated with significant morbidity and mortality due to extensive ectopic mineralization in a variety of tissues. Early diagnosis and multidisciplinary treatment and follow-up in a reference center is of the uttermost importance in order to prevent severe or life-threatening complications. In this review, the clinical presentation, diagnosis and management of primary ectopic mineralization disorders is described.

The present study reports a case of a patient with choroidal neovascularization (CNV) associated with pseudoxanthoma elasticum (PXE). We observed the functional and anatomical improvement of the patient treated with intravitreal vascular endothelial growth factor (VEGF) inhibitor bevacizumab. The study also systematically searched the database for similar cases to provide a literature review. Data concerning the clinical features, treatment strategies and outcomes were extracted and analyzed. Retrospective interventional case report and systematic literature review. A 56-year-old healthy Chinese woman with CNV secondary to PXE was reported. Examinations included best corrected visual acuity (BCVA), biomicroscopy, optical coherence tomography (OCT), fluorescein and indocyanine green angiography and digital fundus photography. The patient managed with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections (bevacizumab 1.25 mg/0.05 mL). The Cochrane Library, PubMed, OVID, and UpToDate databases were searched using the term pseudoxanthoma elasticum or Gronblad-Strandberg syndrome with the limits English. Articles that predated the databases were gathered from current references. Fundus examination revealed angioid streaks bilaterally and CNV in left eye (LE). After the patient underwent three intravitreal injections of bevacizumab, the LE showed absorption of the subretinal fluid and shrinkage of the CNV. Visual acuity (VA) was improved in her treated LE. Bevacizumab treatment was well tolerated with no adverse events reported. Approximately ten articles about 45 patients (49 eyes) describing CNV secondary to angioid streaks in PXE treated with anti-VEGF were found in the literature search. In the present case, bevacizumab of an initial three injection loading dose, achieved maintenance of visual function in the treatment of CNV associated with angioid streaks in PXE. Literature articles concluded that the intravitreal application of anti-VEGF is highly efficient for improving and stabilizing the lesion as well as the eyesight. So we believe that anti-VEGF therapy can be a great choice of treatment for CNV secondary to angioid streaks related PXE.

Two female patients who fulfilled the criteria for &lt;i&gt;L&lt;/i&gt;-tryptophan-induced eosinophilia-myalgia syndrome (EMS) had, together with morphea-like and fasciitis-like sclerotic changes of the skin, lesions that clinically mimicked pseudoxanthoma elasticum (PXE). Histology was compatible with the diagnosis; electron microscopy did not reveal calcium deposits. PXE-like changes may represent an additional feature of the pleomorphic &lt;i&gt;L&lt;/i&gt;-tryptophan-induced EMS.